TW201828963A - Compositions and methods for the induction of cd8+ t-cells - Google Patents

Compositions and methods for the induction of cd8+ t-cells Download PDF

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TW201828963A
TW201828963A TW106145484A TW106145484A TW201828963A TW 201828963 A TW201828963 A TW 201828963A TW 106145484 A TW106145484 A TW 106145484A TW 106145484 A TW106145484 A TW 106145484A TW 201828963 A TW201828963 A TW 201828963A
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Taiwan
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seq
composition
bacterial
bacteroides
subject
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TW106145484A
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Chinese (zh)
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TWI821168B (en
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本田賢也
田上大
服部正平
河上裕
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學校法人慶應義塾
國立大學法人東京大學
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Abstract

Provided herein are compositions and methods for the induction and/or proliferation of CD8+ T-cells. The disclosure also provides methods of treatment of diseases that can be treated by the induction and/or proliferation of CD8+ T-cells.

Description

誘導CD8+　T細胞的組成物及方法Composition and method for inducing CD8 + T cells

本揭示內容係關於用於誘導及/或增殖CD8+ T細胞的組成物及方法。本揭示內容亦提供治療疾病之方法，該等疾病係藉由誘導及/或增殖CD8+ T細胞來治療。The present disclosure relates to compositions and methods for inducing and / or proliferating CD8 + T cells. This disclosure also provides methods of treating diseases that are treated by inducing and / or proliferating CD8 + T cells.

包括人類之動物在包括以下各項之解剖學位置中藏有大量的微生物(共同地稱為微生物群)：口腔、食管、胃、小腸、大腸、盲腸、陰道、皮膚、鼻腔、耳朵及肺。人類微生物群負責大量的關鍵過程，包括免疫系統之發展，碳水化合物、蛋白質及異生物質之代謝，上皮細胞之形成及再生，脂肪儲存，激素之產生，維生素之產生，及病原體感染防護，以及其他(參見，例如，LeBlanc等人 Curr. Opin. Biotechnol. (2013) 24(2):160-168；Hooper等人 Science (2012) 336(6086):1268-1273；Hughes等人 Am. J. Gastroenterol. (2013) 108(7):1066-1074)。可由於諸如抗菌素使用、過度衛生學、飲食、遺傳背景或上述之組合的許多因素引起的人類微生物群之變更已與許多不期望的效應相關聯，該等效應包括以下各項之發生：傳染性疾病(例如，困難梭狀芽孢桿菌(C. difficile)傳染)、發炎、自體免疫及過敏性疾病(例如，潰瘍性結腸炎、克隆氏病、I型糖尿病、食物過敏、哮喘、類風濕性關節炎)及代謝疾病(例如，II型糖尿病、代謝症候群、肥胖症、營養不良)，及癌症以及其他。例如，微生物群之變更可導致針對無害食物抗原或共生細菌抗原的耐量損失、後續過度的發炎反應、代謝失調及對腸內組織之破壞，從而折衷其用作腸腔與體循環之間的阻障的能力。Animals including humans harbor a large number of microorganisms (collectively referred to as microbiota) in anatomical locations including the following: oral cavity, esophagus, stomach, small intestine, large intestine, cecum, vagina, skin, nasal cavity, ears, and lungs. The human microbiome is responsible for a number of key processes, including the development of the immune system, the metabolism of carbohydrates, proteins, and foreign biomass, the formation and regeneration of epithelial cells, the storage of fats, the production of hormones, the production of vitamins, and the protection of pathogen infections, and Others (see, for example, LeBlanc et al. Curr. Opin. Biotechnol. (2013) 24 (2): 160-168; Hooper et al. Science (2012) 336 (6086): 1268-1273; Hughes et al. Am. J. Gastroenterol. (2013) 108 (7): 1066-1074). Changes in the human microbiome that can be caused by many factors such as antibiotic use, excessive hygiene, diet, genetic background, or a combination of the above have been linked to many undesirable effects, including the occurrence of: infectious Diseases (e.g. C. difficile infection), inflammation, autoimmune and allergic diseases (e.g. ulcerative colitis, Crohn's disease, type I diabetes, food allergies, asthma, rheumatoid Arthritis) and metabolic diseases (eg, type II diabetes, metabolic syndrome, obesity, malnutrition), and cancer, among others. For example, changes in the microbiota can lead to loss of tolerance to harmless food antigens or symbiotic bacterial antigens, subsequent excessive inflammatory responses, metabolic disorders, and damage to the intestinal tissue, thus compromising its use as a barrier between the intestinal cavity and systemic circulation Ability.

免疫反應之操縱在治療癌症及疫苗接種方面極具重要性。靶向免疫系統之癌症療法在存活率方面已獲得改良。然而，大百分比之患者對癌症免疫療法不反應。類似地，大的人群子集(例如，老年人)無法對疫苗得到強的免疫反應。The manipulation of immune responses is extremely important in the treatment of cancer and vaccination. Cancer therapies that target the immune system have improved survival. However, a large percentage of patients do not respond to cancer immunotherapy. Similarly, a large subset of the population (e.g., the elderly) cannot get a strong immune response to the vaccine.

用於對抗微生物群變更對健康之有害效應的方法是有限的，儘管此等變更在促進人類病理學方面起到作用。已知調節微生物群的干預方式包括抗生素、益生元、益生菌及糞便移植，其中每一者具有限制及潛在的不利效應。明顯需要對抗微生物群變更對人類健康之有害效應的另外方法。此外，亦需要用於促進對癌症及對疫苗的更強免疫反應的方法。The methods used to combat the adverse health effects of changes in the microbiome are limited, although such changes play a role in promoting human pathology. Interventions known to regulate the microbiome include antibiotics, prebiotics, probiotics, and fecal transplants, each of which has limitations and potential adverse effects. There is clearly a need for additional approaches to counteract the harmful effects of microbiological changes on human health. In addition, methods for promoting a stronger immune response to cancer and vaccines are also needed.

發明人在2016年加入了日本醫學研究及開發機構(Agency for Medical Research and Development；AMED)之創新型先進研究與開發支援項目孵化，該機構之研究及開發主題命名為「使用腸內細菌菌株混合物產生新藥」(AMED-LEAP研究計畫)，且作為AMED-LEAP研究計畫之結果獲得本發明。The inventor joined the incubation of an innovative advanced research and development support project of the Agency for Medical Research and Development (AMED) in 2016. The research and development theme of the agency was named "Using a mixture of intestinal bacteria strains" "Generate a new drug" (AMED-LEAP research project) and obtain the present invention as a result of the AMED-LEAP research project.

本揭示內容係關於細菌菌株之組成物及藉由投與該些組成物誘導及/或增殖CD8+ T細胞的方法。本揭示內容亦提供用於治療疾病之組成物及方法，該等疾病可藉由誘導及/或增殖CD8+ T細胞治療。可藉由誘導及/或增殖CD8+ T細胞治療的疾病包括傳染性疾病及癌症。The present disclosure relates to compositions of bacterial strains and methods for inducing and / or proliferating CD8 + T cells by administering these compositions. This disclosure also provides compositions and methods for treating diseases that can be treated by inducing and / or proliferating CD8 + T cells. Diseases that can be treated by inducing and / or proliferating CD8 + T cells include infectious diseases and cancer.

如本文所揭示的，首次提供了人類來源之細菌菌株之組成物，其經由誘導產生CD8+ T細胞(本文中亦稱為IFNγ+CD8+ T細胞、CD8+ IFNγ+T細胞、CD8+ T細胞或CD8陽性T細胞)之干擾素γ來活化免疫系統。儘管先前已報告用於誘導增殖或累積調節性T細胞之基於微生物的組成物(WO2011/152566)及用於誘導Th17細胞之組成物(WO2015/156419)，本揭示內容首次報告誘發IFNγ+CD8+ T細胞之微生物物質。IFNγ+CD8+ T細胞在免疫系統中起到重要作用，尤其在感染(例如，病毒感染)及癌細胞發展之監視中如此。本文提供的組成物可因此用於例如傳染性疾病之治療及癌症免疫療法。As disclosed herein, for the first time, a composition of a bacterial strain of human origin is provided which induces the production of CD8 + T cells (also referred to herein as IFNγ + CD8 + T cells, CD8 + IFNγ + T cells, CD8 + T cells, or CD8 positive T Cells) to activate the immune system. Although a microbial-based composition for inducing proliferation or accumulation of regulatory T cells (WO2011 / 152566) and a composition for inducing Th17 cells (WO2015 / 156419) have been previously reported, this disclosure first reports the induction of IFNγ + CD8 + T The microbial substance of the cell. IFNγ + CD8 + T cells play an important role in the immune system, especially in the monitoring of infections (eg, viral infections) and the development of cancer cells. The compositions provided herein can therefore be used, for example, in the treatment of infectious diseases and cancer immunotherapy.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌(Phascolarctobacterium faecium)、潰瘍梭桿菌(Fusobacterium ulcerans)、多利擬桿菌(Bacteroides dorei)、單形擬桿菌(Bacteroides uniformis)、罕見小球菌屬(Subdoligranulum sp.)、Paraprevotella xylaniphila、約氏副擬桿菌(Parabacteroides johnsonii)、別樣桿菌屬(Alistipes sp.)、戈登副擬桿菌(Parabacteroides gordonii)、黏液真桿菌(Eubacterum limosum)、狄氏副擬桿菌(Parabacteroides distasonis)、解纖維素擬桿菌(Bacteroides cellulosilyticus)、克拉氏擬桿菌(Bacteroides clarus)、糞厭氧棒狀菌(Anaerostipes caccae)、塞爾氏擬桿菌(Bacteroides salyersiae)、脆弱擬桿菌(Bacteroides fragilis)、單形擬桿菌(Bacteroides uniformis)、埃氏擬桿菌(Bacteroides eggerthii)、梭菌屬(Clostridium sp.)、古氏副擬桿菌(Parabacteroides goldsteinii)、擬桿菌屬(Bacteroides sp.)、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌(Clostridium lavalense)、瘤胃球菌屬(Ruminococcus sp.)及無害芽胞梭菌(Clostridium innocuum)。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Phascolarctobacterium faecium, ulcer Fusobacterium ulcerans, Bacteroides dorei, Bacteroides uniformis, Subdoligranulum sp., Paraprevotella xylaniphila, Parabacteroides johnsonii (Alistipes sp.), Parabacteroides gordonii, Eubacterum limosum, Parabacteroides distasonis, Bacteroides cellulosilyticus, Bacteroides cla Bacteroides clarus), Anaerostipes caccae, Bacteroides salyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroides eggerthii Clostridium sp., Parabac teroides goldsteinii), Bacteroides sp., Trichomonas bacteria HGA0140, Hungatella hathewayi, Clostridium lavalense, Ruminococcus sp. and Clostridium innocuum. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 , At least 23, at least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株： 糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of : Koala faecalis, Clostridium ulcer Bacillus, B. doryi, B. monomorpha, R. micrococcus, Paraprevotella xylaniphila, B. yojei, Isoformis, B. gordonii, Eumycobacterium myxobacteria, B. mycoides, B. dirichi, Cellulolytic Bacillus, B. clarkii, Anaerobic corynebacterium, B. sels, B. fragile, B. haploid, B. escherichia, Clostridium, B. archaea, B. bacterium, Wool spiral Mycobacteria HGA0140, Hungatella hathewayi, Clostridium lavas, Rumenococcus and Clostridium harmless. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer, Dolly Bacteroides, Bacteroides spp., Rare Micrococcus, Paraprevotella xylaniphila, Bacteroides yojei, Allobacterium, Pseudomonas gordonii, Eubacillus myxoides, Pseudomonas diescherii, B. cellulolyticus, Carat Bacteroides spp., Anaerobic Corynebacterium faecalis, B. selenoides, B. fragile, B. haplotypes, B. escherichia, Clostridium, B. archaea and B. bacterium. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer Bacillus, B. doryi, B. monomorpha, R. micrococcus, Paraprevotella xylaniphila, B. yojei, Isoformis, B. gordonii, Eumycobacterium myxobacteria, B. mycoides, B. dirichi, Cellulolytic Bacillus, B. clarkii, Anaerobic corynebacterium, B. selenoides, B. fragile, B. haploid, B. escherichia, Clostridium, B. archaea and B. bacterium. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer, Dolly Bacteroides, Bacteroides spp., Rare micrococcus, Paraprevotella xylaniphila, B. yojei, Isoformis, B. gordonii, E. myxoides and B. dirichi. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising Koala faecalis, Clostridium ulcerans, Bacteroides dorsii, Bacteroides monomorphum, Rare micrococcus, Paraprevotella xylaniphila, about Paracoccus spp., Allobacterium spp., Paracoccus gordonii, Eubacillus mucus and Paracoccus difficile.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of: Koala faecalis, Clostridium ulcerans, Bacteroides doelis, Bacteroides monomorphum, Rare micrococcus , Paraprevotella xylaniphila, B. yojei, Isobacterium, B. gordonii, E. myxobacteria, and B. dirichi.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物基本上由以下各項組成：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting essentially of: Koala faecalis, Clostridium ulcerans, Bacteroides doelis, Bacteroides uniformis, rare small Coccus spp., Paraprevotella xylaniphila, B. yojei, Isoformis spp., G. gordonii, E. myxobacteria, and B. dickii.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、考拉桿菌屬CAG:207、潰瘍梭桿菌、可變梭桿菌(Fusobacterium varium)、多利擬桿菌、福魯克斯擬桿菌(Bacteroides fluxus)、單形擬桿菌、擬桿菌屬D20、罕見小球菌屬、Ruthenibacterium lactatiformans、瘤胃菌科細菌cv2、Gemminger formicilis、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、替莫尼斯別樣桿菌(Alistipes timonensis)、塞內加爾別樣桿菌(Alistipes senegalesis)、戈登副擬桿菌、副擬桿菌屬HGS0025、黏液真桿菌、副擬桿菌屬CAG:2及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Koala genus CAG : 207, Clostridium ulcer, Fusobacterium varium, Bacteroides doloris, Bacteroides fluxus, Bacteroides morphogenes, Bacteroides D20, Rare micrococcus, Ruthenibacterium lactatiformans, Rumen Mycobacteria cv2, Gemminger formicilis, Paraprevotella xylaniphila, Paramycobacterium yojei, Isobacterium, Alistipes timonensis, Alistipes senegalesis, Paragenetic bacteria, Paramiomycetes Bacillus genus HGS0025, Eumycobacterium myxoidum, CAG: 2 and B. dickii. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含： 1) 糞考拉桿菌或考拉桿菌屬CAG:207， 2) 潰瘍梭桿菌或可變梭桿菌， 3) 多利擬桿菌或福魯克斯擬桿菌， 4) 單形擬桿菌或擬桿菌屬D20， 5) 罕見小球菌屬、Ruthenibacterium lactatiformans、瘤胃菌科細菌cv2或Gemminger formicilis， 6) Paraprevotella xylaniphila， 7) 約氏副擬桿菌， 8) 別樣桿菌屬、替莫尼斯別樣桿菌或塞內加爾別樣桿菌， 9) 戈登副擬桿菌或副擬桿菌屬HGS0025， 10) 黏液真桿菌，及 11) 副擬桿菌屬CAG:2或狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising: 1) Koala faecalis or Koala bacterium CAG: 207, 2) Clostridium ulcer or Clostridium mutans, 3) Bacteroides doris or B. fuchsii, 4) Bacteroides or Bacteroides D20, 5) Rare micrococcus, Ruthenibacterium lactatiformans, ruminal bacteria cv2 or Gemminger formicilis, 6) Paraprevotella xylaniphila, 7 ) Pseudomonas yojei, 8) Pseudomonas spp., Pseudomonas timmonis or Pseudomonas senegal, 9) Pseudomonas gordonii or Pseudomonas spp. HGS0025, 10) Eumycobacterium myxoides, and 11) Bacteroides CAG: 2 or Para.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成： 1) 糞考拉桿菌或考拉桿菌屬CAG:207， 2) 潰瘍梭桿菌或可變梭桿菌， 3) 多利擬桿菌或福魯克斯擬桿菌， 4) 單形擬桿菌或擬桿菌屬D20， 5) 罕見小球菌屬、Ruthenibacterium lactatiformans、瘤胃菌科細菌cv2或Gemminger formicilis， 6) Paraprevotella xylaniphila， 7) 約氏副擬桿菌， 8) 別樣桿菌屬、替莫尼斯別樣桿菌或塞內加爾別樣桿菌， 9) 戈登副擬桿菌或副擬桿菌屬HGS0025， 10) 黏液真桿菌，及 11) 副擬桿菌屬CAG:2或狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of: 1) Koala faecalis or Koalabacterium CAG: 207, 2) Clostridium ulcer or Clostridium mutans, 3) Bacteroides doris or B. fuchsii, 4) Bacteroides or Bacteroides D20, 5) Rare micrococcus, Ruthenibacterium lactatiformans, ruminal bacteria cv2 or Gemminger formicilis, 6) Paraprevotella xylaniphila, 7) Pseudomonas yojei, 8) Pseudomonas spp., Pseudomonas timmonis or Pseudomonas senegal, 9) Pseudomonas gordonii or P. parasiticus HGS0025, 10) Eumycobacterium myxoides, And 11) CAG: 2 or Para.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、可變梭桿菌、多利擬桿菌、單形擬桿菌、Ruthenibacterium lactatiformans、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium mutans, B. doryi, B. haplotype, Ruthenibacterium lactatiformans, Paraprevotella xylaniphila, B. yojei, B. senegalensis, B. gordonii, E. myxoides, and B. dirichi In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含糞考拉桿菌、可變梭桿菌、多利擬桿菌、單形擬桿菌、Ruthenibacterium lactatiformans、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising Koala faecalis, Clostridium mutans, Bifidobacterium dorisi, Bacteroides morphogenes, Ruthenibacterium lactatiformans, Paraprevotella xylaniphila, Yossi Paramycobacterium spp., Senegalese bacterium, Paramycobacterium gordonii, Eumycobacterium myxoidans, and Paramycobacterium dirichli.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成：糞考拉桿菌、可變梭桿菌、多利擬桿菌、單形擬桿菌、Ruthenibacterium lactatiformans、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a mixture of purified bacteria, the purified mixture of bacteria consisting of: Koala faecalis, Clostridium mutans, Bacteroides polymorpha, Bacteroides monomorphum, Ruthenibacterium lactatiformans, Paraprevotella xylaniphila, B. yojei, B. senegalensis, B. gordonii, E. myxobacteria, and B. dirichi.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物基本上由以下各項組成：糞考拉桿菌、可變梭桿菌、多利擬桿菌、單形擬桿菌、Ruthenibacterium lactatiformans、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a mixture of purified bacteria, the purified mixture of bacteria consisting essentially of: Koala faecalis, Clostridium mutans, Bacteroides doelis, Bacteroides uniformis, Ruthenibacterium lactatiformans, Paraprevotella xylaniphila, B. yojei, B. senegalensis, B. gordonii, E. myxobacteria, and B. dirichi.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：考拉桿菌屬CAG:207、潰瘍梭桿菌、多利擬桿菌、擬桿菌屬D20、瘤胃菌科細菌cv2、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、副擬桿菌屬HGS0025、黏液真桿菌及副擬桿菌屬CAG:2。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala bacterium CAG: 207, Fusarium ulcer Bacillus, B. doryi, Bacteroides D20, rumenaceae bacteria cv2, Paraprevotella xylaniphila, Parabacter yojei, B. senegalensis, Bacteroides genus HGS0025, Eumycobacterium myxoids and CAG: 2. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含考拉桿菌屬CAG:207、潰瘍梭桿菌、多利擬桿菌、擬桿菌屬D20、瘤胃菌科細菌cv2、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、副擬桿菌屬HGS0025、黏液真桿菌及副擬桿菌屬CAG:2。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising Koalas CAG: 207, Clostridium ulcerans, Bacteroides dorisi, Bacteroides D20, Rumenaceae bacteria cv2, Paraprevotella xylaniphila, Pseudomonas yojei, Pseudomonas senegales, Pseudomonas HGS0025, Eumycobacterium myxoides and CAG: 2.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成：考拉桿菌屬CAG:207、潰瘍梭桿菌、多利擬桿菌、擬桿菌屬D20、瘤胃菌科細菌cv2、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、副擬桿菌屬HGS0025、黏液真桿菌及副擬桿菌屬CAG:2。In one aspect, the present disclosure provides a composition comprising a mixture of purified bacteria, the purified mixture of bacteria consisting of: Koala CAG: 207, Clostridium ulcerans, Bacteroides doris, Bacteroides D20, rumen The mycobacterial bacteria cv2, Paraprevotella xylaniphila, Parabacter yojei, Albinobacterium senegal, Homogeneus HGS0025, Eumycobacterium myxoidum and CAG: 2.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物基本上由以下各項組成：考拉桿菌屬CAG:207、潰瘍梭桿菌、多利擬桿菌、擬桿菌屬D20、瘤胃菌科細菌cv2、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、副擬桿菌屬HGS0025、黏液真桿菌及副擬桿菌屬CAG:2。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting essentially of the following: Koalas CAG: 207, Clostridium ulcerans, Bacteroides doris, Bacteroides D20 , Rumenaceae bacteria cv2, Paraprevotella xylaniphila, Parabacter yojei, Albino senegal, Paramycobacteria HGS0025, Eumycobacterium myxobacteria and CAG: 2.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer Bacillus, B. doryi, B. monomorpha, R. micrococcus, Paraprevotella xylaniphila, B. yojei, I. bacterium, B. gordonii, E. myxoides and B. dirichi. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、考拉桿菌屬CAG:207、潰瘍梭桿菌、可變梭桿菌、多利擬桿菌、福魯克斯擬桿菌、單形擬桿菌、擬桿菌屬D20、罕見小球菌屬、Ruthenibacterium lactatiformans、瘤胃菌科細菌cv2、Gemminger formicilis、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、替莫尼斯別樣桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、副擬桿菌屬HGS0025、黏液真桿菌、副擬桿菌屬CAG:2及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, koala Bacillus CAG: 207, Clostridium ulcerans, Clostridium mutans, Bacteroides doelis, B. fuchsii, B. monomorpha, Bacteroides D20, Rare micrococcus, Ruthenibacterium lactatiformans, Rumenaceae bacteria cv2, Gemminger formicilis, Paraprevotella xylaniphila, Parabivois yojei, Isobacterium, Timonis : 2 and B. dickii. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、可變梭桿菌、多利擬桿菌、單形擬桿菌、Ruthenibacterium lactatiformans、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, variable Clostridium, B. doryi, B. monomorpha, Ruthenibacterium lactatiformans, Paraprevotella xylaniphila, B. yojei, P. senegalensis, P. gordonii, Pseudomonas myxobacteria, and P. dirichi In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：考拉桿菌屬CAG:207、潰瘍梭桿菌、多利擬桿菌、擬桿菌屬D20、瘤胃菌科細菌cv2、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、副擬桿菌屬HGS0025、黏液真桿菌及副擬桿菌屬CAG:2。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala bacterium CAG: 207 , Clostridium ulcerans, Bacterium dorisi, Bacteroides D20, rumenaceae bacteria cv2, Paraprevotella xylaniphila, Parabacter yojei, Alternaria senegal, Paramycobacteria HGS0025, Eumycobacterium myxoides and CAG paramycobacterium 2. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: B. cellulolyticus, B. clarkii , Anaerobic Corynebacterium, Bacteroides selenoides, Bacteroides fragile, Bacteroides morphogenes, Bacteroides escherichia, Clostridium, Pseudomonas archaea, Bacteroides, Trichomonas bacteria HGA0140, Hungatella hathewayi, Clostridium lavas, rumenococcus and harmless Clostridium. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least Ten, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Bacterobacterium cellulolyticus, Carat Bacteroides spp., Anaerobic faecalis, Bacteroides selenoides, B. fragile, B. haplotypes, B. escherichia, Clostridium, B. archaea, Bacteroides, Trichomonas bacteria HGA0140, Hungatella hathewayi, Clostridium lavas, Rumenococcus and Clostridium harmless. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: B. cellulolyticus, B. clarkii , Anaerobic Corynebacterium, Bacteroides selenoides, Bacteroides fragile, Bacteroides morphogenes, Bacteroides escherichia, Clostridium, B. archaea and Bacteroides. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Bacterobacterium cellulolyticus, Carat Bacteroides spp., Anaerobic Corynebacterium faecalis, B. selenoides, B. fragile, B. haplotypes, B. escherichia, Clostridium, B. archaea and B. bacterium In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、罕見小球菌屬及黏液真桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer, rare Micrococcus and Eumycobacterium mucus. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、罕見小球菌屬及黏液真桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer Bacillus, Rare Micrococcus and Eumycobacterium myxoidum. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：多利擬桿菌、單形擬桿菌、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Bacteroides polymorpha, Bacteroides monomorphum, Paraprevotella xylaniphila, B. yojei, Isobacterium, P. gordonii, and B. dickii. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：多利擬桿菌、單形擬桿菌、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Bacteroides doelis, P. monomorpha Bacillus spp., Paraprevotella xylaniphila, B. yoichii, Isobacterium spp., B. gordonii, and B. dickensii. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17.SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 , At least 23, at least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17.SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 , At least 23, at least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO : 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO : 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO : 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID N0:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO : 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17. SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17. SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61 , SEQ ID NO: 62, SEQ ID NO: 63 or SEQ ID NO: 64. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain comprising a 16S rDNA sequence having at least 97% homology to the following: SEQ ID NO : 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 SEQ ID NO: 10 and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含： 1) 包含與SEQ ID NO:1具有至少97%同源性之16S rDNA序列的細菌菌株， 2) 包含與SEQ ID NO:2具有至少97%同源性之16S rDNA序列的細菌菌株， 3) 包含與SEQ ID NO:3具有至少97%同源性之16S rDNA序列的細菌菌株， 4) 包含與SEQ ID NO:4具有至少97%同源性之16S rDNA序列的細菌菌株， 5) 包含與SEQ ID NO:5具有至少97%同源性之16S rDNA序列的細菌菌株， 6) 包含與SEQ ID NO:6具有至少97%同源性之16S rDNA序列的細菌菌株， 7) 包含與SEQ ID NO:7具有至少97%同源性之16S rDNA序列的細菌菌株， 8) 包含與SEQ ID NO:8具有至少97%同源性之16S rDNA序列的細菌菌株， 9) 包含與SEQ ID NO:9具有至少97%同源性之16S rDNA序列的細菌菌株， 10) 包含與SEQ ID NO:10具有至少97%同源性之16S rDNA序列的細菌菌株，及 11) 包含與SEQ ID NO:11具有至少97%同源性之16S rDNA序列的細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising: 1) a bacterial strain comprising a 16S rDNA sequence having at least 97% homology with SEQ ID NO: 1, 2) A bacterial strain comprising a 16S rDNA sequence having at least 97% homology with SEQ ID NO: 2, 3) a bacterial strain comprising a 16S rDNA sequence having at least 97% homology with SEQ ID NO: 3, 4) comprising a SEQ ID NO: 4 a bacterial strain having a 16S rDNA sequence with at least 97% homology, 5) a bacterial strain containing a 16S rDNA sequence with at least 97% homology to SEQ ID NO: 5, 6) a bacterial strain containing NO: 6 a bacterial strain having a 16S rDNA sequence with at least 97% homology, 7) a bacterial strain containing a 16S rDNA sequence with at least 97% homology to SEQ ID NO: 7, 8) a bacterial strain containing SEQ ID NO: 8 a bacterial strain having a 16S rDNA sequence with at least 97% homology, 9) a bacterial strain containing a 16S rDNA sequence with at least 97% homology to SEQ ID NO: 9, 10) a bacterial strain having Bacterial strains with at least 97% homology to 16S rDNA sequences, and 11) Q ID NO: 11 A bacterial strain with a 16S rDNA sequence that is at least 97% homologous.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由細菌菌株組成，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having at least 97% homology to the following: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9. SEQ ID NO: 10 and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成： 1) 包含與SEQ ID NO:1具有至少97%同源性之16S rDNA序列的細菌菌株， 2) 包含與SEQ ID NO:2具有至少97%同源性之16S rDNA序列的細菌菌株， 3) 包含與SEQ ID NO:3具有至少97%同源性之16S rDNA序列的細菌菌株， 4) 包含與SEQ ID NO:4具有至少97%同源性之16S rDNA序列的細菌菌株， 5) 包含與SEQ ID NO:5具有至少97%同源性之16S rDNA序列的細菌菌株， 6) 包含與SEQ ID NO:6具有至少97%同源性之16S rDNA序列的細菌菌株， 7) 包含與SEQ ID NO:7具有至少97%同源性之16S rDNA序列的細菌菌株， 8) 包含與SEQ ID NO:8具有至少97%同源性之16S rDNA序列的細菌菌株， 9) 包含與SEQ ID NO:9具有至少97%同源性之16S rDNA序列的細菌菌株， 10) 包含與SEQ ID NO:10具有至少97%同源性之16S rDNA序列的細菌菌株，及 11) 包含與SEQ ID NO:11具有至少97%同源性之16S rDNA序列的細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of: 1) a bacterium comprising a 16S rDNA sequence having at least 97% homology to SEQ ID NO: 1 A strain, 2) a bacterial strain comprising a 16S rDNA sequence having at least 97% homology with SEQ ID NO: 2, 3) a bacterial strain comprising a 16S rDNA sequence having at least 97% homology with SEQ ID NO: 3, 4) a bacterial strain containing a 16S rDNA sequence having at least 97% homology with SEQ ID NO: 4, 5) a bacterial strain containing a 16S rDNA sequence having at least 97% homology with SEQ ID NO: 5, 6) A bacterial strain comprising a 16S rDNA sequence having at least 97% homology with SEQ ID NO: 6, 7) a bacterial strain comprising a 16S rDNA sequence having at least 97% homology with SEQ ID NO: 7, 8) comprising a SEQ ID NO: 8 a bacterial strain having a 16S rDNA sequence with at least 97% homology, 9) a bacterial strain containing a 16S rDNA sequence with at least 97% homology to SEQ ID NO: 9, 10) containing a sequence with SEQ ID NO NO: 10 Bacterial strain with 16S rDNA sequence of at least 97% homology And 11) comprising SEQ ID NO: 11 bacterial strains having at least 97% homologous to the 16S rDNA sequences.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少99%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 99% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO : 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 SEQ ID NO: 10 and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株，該等細菌菌株包含與以下各項具有至少99%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity to: SEQ ID NO : 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 SEQ ID NO: 10 and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含： 1) 包含與SEQ ID NO:1具有至少97%序列一致性之16S rDNA序列的細菌菌株， 2) 包含與SEQ ID NO:2具有至少97%序列一致性之16S rDNA序列的細菌菌株， 3) 包含與SEQ ID NO:3具有至少97%序列一致性之16S rDNA序列的細菌菌株， 4) 包含與SEQ ID NO:4具有至少97%序列一致性之16S rDNA序列的細菌菌株， 5) 包含與SEQ ID NO:5具有至少97%序列一致性之16S rDNA序列的細菌菌株， 6) 包含與SEQ ID NO:6具有至少97%序列一致性之16S rDNA序列的細菌菌株， 7) 包含與SEQ ID NO:7具有至少97%序列一致性之16S rDNA序列的細菌菌株， 8) 包含與SEQ ID NO:8具有至少97%序列一致性之16S rDNA序列的細菌菌株， 9) 包含與SEQ ID NO:9具有至少97%序列一致性之16S rDNA序列的細菌菌株， 10) 包含與SEQ ID NO:10具有至少97%序列一致性之16S rDNA序列的細菌菌株，及 11) 包含與SEQ ID NO:11具有至少97%序列一致性之16S rDNA序列的細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising: 1) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 1, 2) A bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 2, 3) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 3, 4) comprising a SEQ ID NO: 4 a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, 5) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 5, 6) comprising a sequence NO: 6 a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, 7) a bacterial strain containing a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 7, 8) containing a bacterial strain identical to SEQ ID NO: 8 a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, 9) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 9, 10) comprising a bacterial strain having a sequence identity with SEQ ID NO: 10 At least 97% sequence identity A bacterial strain of 16S rDNA sequence, and 11) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含： 1) 包含與SEQ ID NO:1具有至少99%序列一致性之16S rDNA序列的細菌菌株， 2) 包含與SEQ ID NO:2具有至少99%序列一致性之16S rDNA序列的細菌菌株， 3) 包含與SEQ ID NO:3具有至少99%序列一致性之16S rDNA序列的細菌菌株， 4) 包含與SEQ ID NO:4具有至少99%序列一致性之16S rDNA序列的細菌菌株， 5) 包含與SEQ ID NO:5具有至少99%序列一致性之16S rDNA序列的細菌菌株， 6) 包含與SEQ ID NO:6具有至少99%序列一致性之16S rDNA序列的細菌菌株， 7) 包含與SEQ ID NO:7具有至少99%序列一致性之16S rDNA序列的細菌菌株， 8) 包含與SEQ ID NO:8具有至少99%序列一致性之16S rDNA序列的細菌菌株， 9) 包含與SEQ ID NO:9具有至少99%序列一致性之16S rDNA序列的細菌菌株， 10) 包含與SEQ ID NO:10具有至少99%序列一致性之16S rDNA序列的細菌菌株，及 11) 包含與SEQ ID NO:11具有至少99%序列一致性之16S rDNA序列的細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising: 1) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 1, 2) A bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 2, 3) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 3, 4) comprising a SEQ ID NO: 4 a bacterial strain having a 16S rDNA sequence having at least 99% sequence identity, 5) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 5, 6) comprising a sequence NO: 6 a bacterial strain having a 16S rDNA sequence having at least 99% sequence identity, 7) a bacterial strain containing a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 7, 8) containing a bacterial strain identical to SEQ ID NO: 8 a bacterial strain having a 16S rDNA sequence having at least 99% sequence identity, 9) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 9, 10) comprising a bacterial strain having a sequence identity with SEQ ID NO: 10 At least 99% sequence identity A bacterial strain of 16S rDNA sequence, and 11) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株，該等細菌菌株包含具有以下各項之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain comprising a 16S rDNA sequence having the following: SEQ ID NO: 1, SEQ ID NO: 2.SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由細菌菌株組成，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the following: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9. SEQ ID NO: 10 and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由細菌菌株組成，該等細菌菌株包含與以下各項具有至少99%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9. SEQ ID NO: 10 and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成： 1) 包含與SEQ ID NO:1具有至少97%序列一致性之16S rDNA序列的細菌菌株， 2) 包含與SEQ ID NO:2具有至少97%序列一致性之16S rDNA序列的細菌菌株， 3) 包含與SEQ ID NO:3具有至少97%序列一致性之16S rDNA序列的細菌菌株， 4) 包含與SEQ ID NO:4具有至少97%序列一致性之16S rDNA序列的細菌菌株， 5) 包含與SEQ ID NO:5具有至少97%序列一致性之16S rDNA序列的細菌菌株， 6) 包含與SEQ ID NO:6具有至少97%序列一致性之16S rDNA序列的細菌菌株， 7) 包含與SEQ ID NO:7具有至少97%序列一致性之16S rDNA序列的細菌菌株， 8) 包含與SEQ ID NO:8具有至少97%序列一致性之16S rDNA序列的細菌菌株， 9) 包含與SEQ ID NO:9具有至少97%序列一致性之16S rDNA序列的細菌菌株， 10) 包含與SEQ ID NO:10具有至少97%序列一致性之16S rDNA序列的細菌菌株，及 11) 包含與SEQ ID NO:11具有至少97%序列一致性之16S rDNA序列的細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of: 1) a bacterium comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 1 A strain, 2) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 2, 3) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 3, 4) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 4, 5) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 5, 6) A bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 6, 7) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 7, 8) comprising a SEQ ID NO: 8 a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, 9) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 9, 10) comprising a sequence NO: 10 has at least 97% sequence identity 16S rDNA sequence of a bacterial strain, and 11) comprising SEQ ID NO: 11 bacterial strain having 16S rDNA sequence of at least 97% sequence identity.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成： 1) 包含與SEQ ID NO:1具有至少99%序列一致性之16S rDNA序列的細菌菌株， 2) 包含與SEQ ID NO:2具有至少99%序列一致性之16S rDNA序列的細菌菌株， 3) 包含與SEQ ID NO:3具有至少99%序列一致性之16S rDNA序列的細菌菌株， 4) 包含與SEQ ID NO:4具有至少99%序列一致性之16S rDNA序列的細菌菌株， 5) 包含與SEQ ID NO:5具有至少99%序列一致性之16S rDNA序列的細菌菌株， 6) 包含與SEQ ID NO:6具有至少99%序列一致性之16S rDNA序列的細菌菌株， 7) 包含與SEQ ID NO:7具有至少99%序列一致性之16S rDNA序列的細菌菌株， 8) 包含與SEQ ID NO:8具有至少99%序列一致性之16S rDNA序列的細菌菌株， 9) 包含與SEQ ID NO:9具有至少97%序列一致性之16S rDNA序列的細菌菌株， 10) 包含與SEQ ID NO:10具有至少99%序列一致性之16S rDNA序列的細菌菌株，及 11) 包含與SEQ ID NO:11具有至少99%序列一致性之16S rDNA序列的細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of: 1) a bacterium comprising a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 1 A strain, 2) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 2, 3) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 3, 4) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 4, 5) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 5, 6) A bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 6, 7) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 7, 8) comprising a SEQ ID NO: 8 a bacterial strain having a 16S rDNA sequence with at least 99% sequence identity, 9) a bacterial strain containing a 16S rDNA sequence with at least 97% sequence identity to SEQ ID NO: 9, 10) containing a sequence ID with SEQ ID NO: 9 NO: 10 has at least 99% sequence identity 16S rDNA sequence of a bacterial strain, and 11) comprising SEQ ID NO: 11 bacterial strain having 16S rDNA sequence of at least 99% sequence identity.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由細菌菌株組成，該等細菌菌株包含具有以下各項之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having the following: SEQ ID NO: 1, SEQ ID NO : 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 And SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61 , SEQ ID NO: 62, SEQ ID NO: 63 or SEQ ID NO: 64. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少99%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 99% sequence identity to rDNA sequence: SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61 , SEQ ID NO: 62, SEQ ID NO: 63 or SEQ ID NO: 64. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID N0:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO : 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62 , SEQ ID NO: 63 or SEQ ID NO: 64.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株，該等細菌菌株包含與以下各項具有至少99%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID N0:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity to: SEQ ID NO : 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62 , SEQ ID NO: 63 or SEQ ID NO: 64.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含： 1) 包含與SEQ ID NO:54具有至少97%序列一致性之16S rDNA序列的細菌菌株， 2) 包含與SEQ ID NO:55具有至少97%序列一致性之16S rDNA序列的細菌菌株， 3) 包含與SEQ ID NO:56具有至少97%序列一致性之16S rDNA序列的細菌菌株， 4) 包含與SEQ ID NO:57具有至少97%序列一致性之16S rDNA序列的細菌菌株， 5) 包含與SEQ ID NO:58具有至少97%序列一致性之16S rDNA序列的細菌菌株， 6) 包含與SEQ ID NO:59具有至少97%序列一致性之16S rDNA序列的細菌菌株， 7) 包含與SEQ ID NO:60具有至少97%序列一致性之16S rDNA序列的細菌菌株， 8) 包含與SEQ ID NO:61具有至少97%序列一致性之16S rDNA序列的細菌菌株， 9) 包含與SEQ ID NO:62具有至少97%序列一致性之16S rDNA序列的細菌菌株， 10) 包含與SEQ ID NO:63具有至少97%序列一致性之16S rDNA序列的細菌菌株，及 11) 包含與SEQ ID NO:64具有至少97%序列一致性之16S rDNA序列的細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising: 1) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 54, 2) A bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 55, 3) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 56, 4) comprising a SEQ ID NO: 57 a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, 5) a bacterial strain containing a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 58, 6) containing a sequence NO: 59 a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, 7) a bacterial strain containing a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 60, 8) containing a bacterial strain identical to SEQ ID NO: 61 a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, 9) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 62, 10) a bacterial strain comprising having a sequence identity with SEQ ID NO: 63 16S r with at least 97% sequence identity A bacterial strain having a DNA sequence, and 11) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 64.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含： 1) 包含與SEQ ID NO:54具有至少99%序列一致性之16S rDNA序列的細菌菌株， 2) 包含與SEQ ID NO:55具有至少99%序列一致性之16S rDNA序列的細菌菌株， 3) 包含與SEQ ID NO:56具有至少99%序列一致性之16S rDNA序列的細菌菌株， 4) 包含與SEQ ID NO:57具有至少99%序列一致性之16S rDNA序列的細菌菌株， 5) 包含與SEQ ID NO:58具有至少99%序列一致性之16S rDNA序列的細菌菌株， 6) 包含與SEQ ID NO:59具有至少99%序列一致性之16S rDNA序列的細菌菌株， 7) 包含與SEQ ID NO:60具有至少99%序列一致性之16S rDNA序列的細菌菌株， 8) 包含與SEQ ID NO:61具有至少99%序列一致性之16S rDNA序列的細菌菌株， 9) 包含與SEQ ID NO:62具有至少99%序列一致性之16S rDNA序列的細菌菌株， 10) 包含與SEQ ID NO:63具有至少99%序列一致性之16S rDNA序列的細菌菌株，及 11) 包含與SEQ ID NO:64具有至少99%序列一致性之16S rDNA序列的細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising: 1) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 54, 2) A bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 55, 3) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 56, 4) comprising a SEQ ID NO: 57 a bacterial strain having a 16S rDNA sequence having at least 99% sequence identity, 5) a bacterial strain containing a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 58, 6) containing a NO: 59 a bacterial strain having a 16S rDNA sequence with at least 99% sequence identity, 7) a bacterial strain containing a 16S rDNA sequence with at least 99% sequence identity, and 8) a SEQ ID NO: 61 a bacterial strain having a 16S rDNA sequence having at least 99% sequence identity, 9) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 62, 10) a bacterial strain comprising having a sequence identity with SEQ ID NO: 63 16S r with at least 99% sequence identity A bacterial strain having a DNA sequence, and 11) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 64.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株，該等細菌菌株包含具有以下各項之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain comprising a 16S rDNA sequence having the following: SEQ ID NO: 54, SEQ ID NO: 55.SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63 or SEQ ID NO: 64.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由細菌菌株組成，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to the following: SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62. SEQ ID NO: 63 or SEQ ID NO: 64.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由細菌菌株組成，該等細菌菌株包含與以下各項具有至少99%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity to: SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62. SEQ ID NO: 63 or SEQ ID NO: 64.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成： 1) 包含與SEQ ID NO:54具有至少97%序列一致性之16S rDNA序列的細菌菌株， 2) 包含與SEQ ID NO:55具有至少97%序列一致性之16S rDNA序列的細菌菌株， 3) 包含與SEQ ID NO:56具有至少97%序列一致性之16S rDNA序列的細菌菌株， 4) 包含與SEQ ID NO:57具有至少97%序列一致性之16S rDNA序列的細菌菌株， 5) 包含與SEQ ID NO:58具有至少97%序列一致性之16S rDNA序列的細菌菌株， 6) 包含與SEQ ID NO:59具有至少97%序列一致性之16S rDNA序列的細菌菌株， 7) 包含與SEQ ID NO:60具有至少97%序列一致性之16S rDNA序列的細菌菌株， 8) 包含與SEQ ID NO:61具有至少97%序列一致性之16S rDNA序列的細菌菌株， 9) 包含與SEQ ID NO:62具有至少97%序列一致性之16S rDNA序列的細菌菌株， 10) 包含與SEQ ID NO:63具有至少97%序列一致性之16S rDNA序列的細菌菌株，及 11) 包含與SEQ ID NO:64具有至少97%序列一致性之16S rDNA序列的細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of: 1) a bacterium comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 54 A strain, 2) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 55, 3) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 56, 4) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 57, 5) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 58, 6) A bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 59, 7) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 60, 8) comprising a SEQ ID NO: 61 a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, 9) a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 62, 10) comprising a sequence NO: 63 has at least 97% sequence Bacterial strains consistency of 16S rDNA sequences, and 11) comprising SEQ ID NO: 64 bacterial strain having 16S rDNA sequence of at least 97% sequence identity.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成： 1) 包含與SEQ ID NO:54具有至少99%序列一致性之16S rDNA序列的細菌菌株， 2) 包含與SEQ ID NO:55具有至少99%序列一致性之16S rDNA序列的細菌菌株， 3) 包含與SEQ ID NO:56具有至少99%序列一致性之16S rDNA序列的細菌菌株， 4) 包含與SEQ ID NO:57具有至少99%序列一致性之16S rDNA序列的細菌菌株， 5) 包含與SEQ ID NO:58具有至少99%序列一致性之16S rDNA序列的細菌菌株， 6) 包含與SEQ ID NO:59具有至少99%序列一致性之16S rDNA序列的細菌菌株， 7) 包含與SEQ ID NO:60具有至少99%序列一致性之16S rDNA序列的細菌菌株， 8) 包含與SEQ ID NO:61具有至少99%序列一致性之16S rDNA序列的細菌菌株， 9) 包含與SEQ ID NO:62具有至少99%序列一致性之16S rDNA序列的細菌菌株， 10) 包含與SEQ ID NO:63具有至少99%序列一致性之16S rDNA序列的細菌菌株，及 11) 包含與SEQ ID NO:64具有至少99%序列一致性之16S rDNA序列的細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of: 1) a bacterium comprising a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 54 A strain, 2) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 55, 3) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 56, 4) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 57, 5) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity with SEQ ID NO: 58, 6) A bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 59, 7) a bacterial strain comprising a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 60, 8) comprising a SEQ ID NO: 61 a bacterial strain having a 16S rDNA sequence having at least 99% sequence identity, 9) a bacterial strain containing a 16S rDNA sequence having at least 99% sequence identity to SEQ ID NO: 62, 10) containing a sequence NO: 63 has at least 99% sequence Bacterial strains consistency of 16S rDNA sequences, and 11) comprising SEQ ID NO: 64 bacterial strain having 16S rDNA sequence of at least 99% sequence identity.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由細菌菌株組成，該等細菌菌株包含具有以下各項之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having the following: SEQ ID NO: 54, SEQ ID NO : 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63 Or SEQ ID NO: 64.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least Ten, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least Ten, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 , SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 , SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 , SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 , SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the disclosure provides a composition comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the following: SEQ ID NO: 12, SEQ ID NO : 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21 . In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 bacterial strains.

在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to the following: SEQ ID NO: 12, SEQ ID NO : 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21 . In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 bacterial strains.

在一個態樣中，本揭示內容提供包含兩種或更多種細菌菌株之組成物，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the disclosure provides a composition comprising two or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to the following: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含兩種或更多種細菌菌株之組成物，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the disclosure provides a composition comprising two or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity with the following: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含兩種或更多種細菌菌株之組成物，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the disclosure provides a composition comprising two or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to the following: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含兩種或更多種細菌菌株之組成物，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the disclosure provides a composition comprising two or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity with the following: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 , At least 23, at least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 , At least 23, at least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO : 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO : 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO : 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO : 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46及SEQ ID NO:47。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46及SEQ ID NO:47。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46及SEQ ID NO:47。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46及SEQ ID NO:47。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46及SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46及SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least Ten, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least Ten, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31, or SEQ ID NO: 36. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31, or SEQ ID NO: 36. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31 or SEQ ID NO: 36. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31 or SEQ ID NO: 36. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31 or SEQ ID NO: 36. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31 or SEQ ID NO: 36. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% sequence identity to: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% homology to rDNA sequence: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%序列一致性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%序列一致性之16S rDNA序列。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 95% sequence identity to rDNA sequence: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the bacterial strain comprises a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the SEQ ID NOs. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在本文提供的組成物之一些實施例中，細菌菌株之至少50%屬於擬桿菌目。在本文提供的組成物之一些實施例中，細菌菌株中之一或多者屬於擬桿菌目，且細菌菌株中之一或多者屬於梭菌目。在本文提供的組成物之一些實施例中，細菌菌株之至少25%屬於擬桿菌科。在本文提供的組成物之一些實施例中，細菌菌株中之一或多者屬於擬桿菌屬。在本文提供的組成物之一些實施例中，該組成物不包括屬於擬桿菌目之細菌菌株。In some embodiments of the compositions provided herein, at least 50% of the bacterial strains belong to the order Bacteroides. In some embodiments of the compositions provided herein, one or more of the bacterial strains belong to the order Bacteroides, and one or more of the bacterial strains belong to the order Clostridia. In some embodiments of the compositions provided herein, at least 25% of the bacterial strains belong to the family Bacteroides. In some embodiments of the compositions provided herein, one or more of the bacterial strains belong to the genus Bacteroides. In some embodiments of the composition provided herein, the composition does not include a bacterial strain belonging to the order Bacteroides.

在本文提供的組成物之一些實施例中，細菌菌株中之一或多者為孢子形成劑。在本文提供的組成物之一些實施例中，細菌菌株中之一或多者係呈孢子形式。在本文提供的組成物之一些實施例中，細菌菌株中之一或多者為非孢子形成劑。在本文提供的組成物之一些實施例中，組成物僅包含絕對厭氧細菌菌株。在本文提供的組成物之一些實施例中，細菌菌株中之一或多者不具有抗生素抗性基因。在本文提供的組成物之一些實施例中，抗生素抗性基因使得細菌菌株對萬古黴素有抗性。在本文提供的組成物之一些實施例中，細菌菌株為人類來源之細菌。在本文提供的組成物之一些實施例中，細菌菌株係來源於多於一種人類供體。在本文提供的組成物之一些實施例中，組成物誘導CD8+T細胞之增殖及/或累積。In some embodiments of the compositions provided herein, one or more of the bacterial strains are spore-forming agents. In some embodiments of the compositions provided herein, one or more of the bacterial strains are in the form of spores. In some embodiments of the compositions provided herein, one or more of the bacterial strains are non-spore-forming agents. In some embodiments of the composition provided herein, the composition comprises only an absolutely anaerobic bacterial strain. In some embodiments of the compositions provided herein, one or more of the bacterial strains do not have an antibiotic resistance gene. In some embodiments of the compositions provided herein, the antibiotic resistance gene renders the bacterial strain resistant to vancomycin. In some embodiments of the compositions provided herein, the bacterial strain is a bacterium of human origin. In some embodiments of the compositions provided herein, the bacterial strain is derived from more than one human donor. In some embodiments of the composition provided herein, the composition induces proliferation and / or accumulation of CD8 + T cells.

在本文提供的組成物之一些實施例中，組成物為醫藥組成物。在本文提供的醫藥組成物之一些實施例中，醫藥組成物包含醫藥學上可接受的賦形劑。在本文提供的醫藥組成物之一些實施例中，醫藥組成物係配製用於口服投與。在本文提供的醫藥組成物之一些實施例中，醫藥組成物係配製用於直腸投與。在本文提供的醫藥組成物之一些實施例中，醫藥組成物係配製用於遞送至腸。在本文提供的醫藥組成物之一些實施例中，醫藥組成物係配製用於遞送至結腸。在本文提供的醫藥組成物之一些實施例中，細菌菌株中之一或多者係凍乾的。在本文提供的醫藥組成物之一些實施例中，醫藥組成物係呈膠囊形式。在本文提供的醫藥組成物之一些實施例中，醫藥組成物進一步包含pH敏感組成物，其包含一或多種腸聚合物。In some embodiments of the composition provided herein, the composition is a pharmaceutical composition. In some embodiments of the pharmaceutical composition provided herein, the pharmaceutical composition comprises a pharmaceutically acceptable excipient. In some embodiments of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for oral administration. In some embodiments of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for rectal administration. In some embodiments of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for delivery to the intestine. In some embodiments of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for delivery to the colon. In some embodiments of the pharmaceutical compositions provided herein, one or more of the bacterial strains are lyophilized. In some embodiments of the pharmaceutical composition provided herein, the pharmaceutical composition is in the form of a capsule. In some embodiments of the pharmaceutical composition provided herein, the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

在一個態樣中，本揭示內容提供包含本文提供的任何組成物及養分的食物產品。In one aspect, the disclosure provides a food product comprising any of the compositions and nutrients provided herein.

在本文提供的組成物之一些實施例中，組成物進一步包含一或多種抗癌劑。在本文提供的組成物之一些實施例中，抗癌劑為化療劑。在本文提供的組成物之一些實施例中，抗癌劑為癌症免疫療法劑。在本文提供的組成物之一些實施例中，癌症免疫療法劑為免疫查核點抑制劑。在本文提供的組成物之一些實施例中，免疫查核點抑制劑為PD-1抑制劑、PD-L-1抑制劑或CTLA-4抑制劑。在本文提供的組成物之一些實施例中，免疫查核點抑制劑為PD-1抑制劑。在本文提供的組成物之一些實施例中，免疫查核點抑制劑為CTLA-4抑制劑。在本文提供的組成物之一些實施例中，組成物進一步包含一或多種細胞介素。在本文提供的組成物之一些實施例中，細胞介素為IL-2、IL-15或IL-21。在本文提供的組成物之一些實施例中，組成物進一步包含一或多種共激劑。在本文提供的組成物之一些實施例中，共激劑為CD-28、OX-40、4-1BB或CD40抗體。In some embodiments of the composition provided herein, the composition further comprises one or more anticancer agents. In some embodiments of the compositions provided herein, the anticancer agent is a chemotherapeutic agent. In some embodiments of the compositions provided herein, the anticancer agent is a cancer immunotherapy agent. In some embodiments of the compositions provided herein, the cancer immunotherapy agent is an immune checkpoint inhibitor. In some embodiments of the compositions provided herein, the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L-1 inhibitor, or a CTLA-4 inhibitor. In some embodiments of the compositions provided herein, the immune checkpoint inhibitor is a PD-1 inhibitor. In some embodiments of the compositions provided herein, the immune checkpoint inhibitor is a CTLA-4 inhibitor. In some embodiments of the composition provided herein, the composition further comprises one or more cytokines. In some embodiments of the compositions provided herein, the interleukin is IL-2, IL-15, or IL-21. In some embodiments of the composition provided herein, the composition further comprises one or more co-stimulants. In some embodiments of the compositions provided herein, the stimulant is a CD-28, OX-40, 4-1BB, or CD40 antibody.

在本文提供的組成物之一些實施例中，組成物進一步包含一或多種疫苗。在本文提供的組成物之一些實施例中，疫苗為樹狀細胞疫苗。在本文提供的組成物之一些實施例中，組成物係與授受性細胞轉移療法組合。在本文提供的組成物之一些實施例中，授受性細胞轉移療法為工程化T細胞受體或嵌合抗原受體之使用。In some embodiments of the composition provided herein, the composition further comprises one or more vaccines. In some embodiments of the compositions provided herein, the vaccine is a dendritic cell vaccine. In some embodiments of the compositions provided herein, the composition is combined with an adaptive cell transfer therapy. In some embodiments of the compositions provided herein, the adaptive cell transfer therapy is the use of an engineered T cell receptor or a chimeric antigen receptor.

在一個態樣中，本揭示內容提供包含本文提供的任何組成物及抗原的疫苗。在本文提供的疫苗之一些實施例中，抗原為HIV抗原。在本文提供的疫苗之一些實施例中，抗原為肝炎抗原。In one aspect, the disclosure provides a vaccine comprising any of the compositions and antigens provided herein. In some embodiments of the vaccines provided herein, the antigen is an HIV antigen. In some embodiments of the vaccines provided herein, the antigen is a hepatitis antigen.

在本文提供的組成物之一些實施例中，組成物進一步包含一或多種消炎劑。在本文提供的組成物之一些實施例中，消炎劑為NSAID。In some embodiments of the composition provided herein, the composition further comprises one or more anti-inflammatory agents. In some embodiments of the compositions provided herein, the anti-inflammatory agent is NSAID.

在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內CD8+ T細胞之增殖及/或累積之誘導。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內的IFN-γ產生增加。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內所投與組成物之一或多種細菌菌株之存在。在本文提供的組成物之一些實施例中，所投與組成物之一或多種細菌菌株先前不存在於該受試者之腸內。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內所投與組成物之一或多種細菌菌株之植入。在本文提供的組成物之一些實施例中，所投與組成物之一或多種細菌菌株先前未植入該受試者之腸內。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內所投與組成物之細菌菌株數量之增加。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致植入於該受試者之腸內的所投與組成物之細菌菌株數量之增加。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內所投與組成物之細菌菌株之細菌量之增加。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致植入於該受試者之腸內的所投與組成物之細菌菌株之細菌量之增加。In some embodiments of the compositions provided herein, administering the composition to a subject results in induction of proliferation and / or accumulation of CD8 + T cells in the intestine of the subject. In some embodiments of the compositions provided herein, administering the composition to a subject results in increased production of IFN-γ in the subject's intestine. In some embodiments of the compositions provided herein, administering the composition to a subject results in the presence of one or more bacterial strains of the composition administered in the intestine of the subject. In some embodiments of the compositions provided herein, one or more bacterial strains of the administered composition were not previously present in the intestine of the subject. In some embodiments of the compositions provided herein, administering the composition to a subject results in implantation of one or more bacterial strains of the composition administered in the intestine of the subject. In some embodiments of the compositions provided herein, one or more bacterial strains of the administered composition have not been previously implanted in the intestine of the subject. In some embodiments of the compositions provided herein, administering the composition to a subject results in an increase in the number of bacterial strains of the composition administered in the subject's intestine. In some embodiments of the compositions provided herein, administering the composition to a subject results in an increase in the number of bacterial strains of the administered composition implanted in the intestine of the subject. In some embodiments of the compositions provided herein, administering the composition to a subject results in an increase in the amount of bacteria of a bacterial strain of the composition administered in the intestine of the subject. In some embodiments of the compositions provided herein, administering the composition to a subject results in an increase in the amount of bacteria of the bacterial strain of the administered composition implanted in the intestine of the subject.

在一個態樣中，本揭示內容提供治療受試者之疾病的方法，其包含以治療該疾病之有效量投與本文提供的任何組成物至該受試者。在本文提供的方法之一些實施例中，將組成物投與至受試者導致在該受試者之腸內CD8+ T細胞之增殖及/或累積之誘導。在本文提供的方法之一些實施例中，該受試者之腸內CD8+ T細胞之增殖及/或累積相較於在該組成物之投與之前在該受試者之腸內CD8+ T細胞之增殖及/或累積而言增加至少10%、至少20%、至少30%、至少40%、至少50%、至少100%或至少200%。在本文提供的方法之一些實施例中，將組成物投與至受試者導致在相較於在該組成物之投與之前該受試者之腸內的IFN-γ產生時該受試者之腸IFN-γ產生之增加。在本文提供的方法之一些實施例中，將組成物投與至受試者導致在相較於在該組成物之投與之前在該受試者之腸內的IFN-γ產生時在該受試者之腸內IFN-γ產生之增加達至少10%、至少20%、至少30%、至少40%、至少50%、至少100%或至少200%。In one aspect, the disclosure provides a method of treating a disease in a subject, comprising administering to the subject any composition provided herein in an amount effective to treat the disease. In some embodiments of the methods provided herein, administering the composition to a subject results in induction of the proliferation and / or accumulation of CD8 + T cells in the intestine of the subject. In some embodiments of the methods provided herein, the proliferation and / or accumulation of CD8 + T cells in the intestine of the subject is greater than that of CD8 + T cells in the intestine of the subject prior to administration of the composition. Proliferation and / or cumulative increase of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 100% or at least 200%. In some embodiments of the methods provided herein, administering the composition to a subject results in the subject being IFN-γ produced in the intestine of the subject compared to prior to administration of the composition. Increased intestinal IFN-γ production. In some embodiments of the methods provided herein, administering the composition to a subject results in the subject receiving IFN-γ in the subject's intestine as compared to prior to administration of the composition. The increase in the intestinal IFN-γ production of the subject was at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 100%, or at least 200%.

在本文提供的方法之一些實施例中，受試者患有癌症。在本文提供的方法之一些實施例中，癌症為惡性腫瘤、神經膠質瘤、間皮瘤、黑素瘤、淋巴瘤、白血病、腺癌、乳癌、卵巢癌、子宮頸癌、神經膠質母細胞瘤、多發性骨髓瘤、前列腺癌、伯基特氏淋巴瘤、頭頸癌、結腸癌、結腸直腸癌、非小細胞肺癌、小細胞肺癌、食管癌、胃癌、胰腺癌、肝膽癌、膽囊癌、小腸癌、直腸癌、腎癌、膀胱癌、前列腺癌、陰莖癌、尿道癌、睾丸癌、陰道癌、子宮癌、甲狀腺癌、副甲狀腺癌、腎上腺癌、胰腺內分泌癌、類癌瘤癌、骨癌、皮膚癌、視網膜母細胞瘤、霍奇金氏淋巴瘤、非霍奇金氏淋巴瘤、卡波西氏肉瘤、多中心Castleman氏病、AIDS相關原發性滲出淋巴瘤、神經外胚層腫瘤或橫紋肌肉瘤。在本文提供的方法之一些實施例中，癌症為前列腺癌、膀胱癌、非小細胞肺癌、泌尿上皮細胞惡性腫瘤、黑素瘤或腎細胞惡性腫瘤。在本文提供的方法之一些實施例中，受試者經歷放射治療。In some embodiments of the methods provided herein, the subject has cancer. In some embodiments of the methods provided herein, the cancer is a malignant tumor, glioma, mesothelioma, melanoma, lymphoma, leukemia, adenocarcinoma, breast cancer, ovarian cancer, cervical cancer, glioblastoma , Multiple myeloma, prostate cancer, Burkitt's lymphoma, head and neck cancer, colon cancer, colorectal cancer, non-small cell lung cancer, small cell lung cancer, esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, gallbladder cancer, small intestine Cancer, rectal cancer, kidney cancer, bladder cancer, prostate cancer, penile cancer, urinary tract cancer, testicular cancer, vaginal cancer, uterine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, pancreatic endocrine cancer, carcinoid tumor, bone cancer , Skin cancer, retinoblastoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, Kaposi's sarcoma, multicenter Castleman's disease, AIDS-related primary exudative lymphoma, neuroectodermal tumor, or Rhabdomyosarcoma. In some embodiments of the methods provided herein, the cancer is prostate cancer, bladder cancer, non-small cell lung cancer, urinary epithelial cell malignancy, melanoma, or renal cell malignancy. In some embodiments of the methods provided herein, the subject undergoes radiation therapy.

在本文提供的方法之一些實施例中，方法進一步包括投與一或多種抗癌劑。在本文提供的方法之一些實施例中，抗癌劑為化療劑。在本文提供的方法之一些實施例中，抗癌劑為癌症免疫療法劑。在本文提供的方法之一些實施例中，癌症免疫療法劑為免疫查核點抑制劑。在本文提供的方法之一些實施例中，免疫查核點抑制劑為PD-1抑制劑、PD-L-1抑制劑或CTLA-4抑制劑。在本文提供的方法之一些實施例中，免疫查核點抑制劑為PD-1抑制劑。在本文提供的方法之一些實施例中，免疫查核點抑制劑為CTLA-4抑制劑。In some embodiments of the methods provided herein, the method further comprises administering one or more anticancer agents. In some embodiments of the methods provided herein, the anticancer agent is a chemotherapeutic agent. In some embodiments of the methods provided herein, the anticancer agent is a cancer immunotherapy agent. In some embodiments of the methods provided herein, the cancer immunotherapy agent is an immune checkpoint inhibitor. In some embodiments of the methods provided herein, the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L-1 inhibitor, or a CTLA-4 inhibitor. In some embodiments of the methods provided herein, the immune checkpoint inhibitor is a PD-1 inhibitor. In some embodiments of the methods provided herein, the immune checkpoint inhibitor is a CTLA-4 inhibitor.

在本文提供的方法之一些實施例中，方法進一步包括投與一或多種細胞介素。在本文提供的方法之一些實施例中，細胞介素為IL-2、IL-15或IL-21。In some embodiments of the methods provided herein, the method further comprises administering one or more cytokines. In some embodiments of the methods provided herein, the interleukin is IL-2, IL-15 or IL-21.

在本文提供的方法之一些實施例中，方法進一步包括投與一或多種共激劑。在本文提供的方法之一些實施例中，共激劑為CD-28、OX-40、4-1BB或CD40抗體。In some embodiments of the methods provided herein, the method further comprises administering one or more co-stimulants. In some embodiments of the methods provided herein, the stimulant is a CD-28, OX-40, 4-1BB, or CD40 antibody.

在本文提供的方法之一些實施例中，方法進一步包括投與一或多種疫苗。在本文提供的方法之一些實施例中，疫苗為樹狀細胞疫苗。In some embodiments of the methods provided herein, the method further comprises administering one or more vaccines. In some embodiments of the methods provided herein, the vaccine is a dendritic cell vaccine.

在本文提供的方法之一些實施例中，方法進一步包括投與授受性細胞轉移療法。在本文提供的方法之一些實施例中，授受性細胞轉移療法為工程化T細胞受體或嵌合抗原受體之使用。In some embodiments of the methods provided herein, the method further comprises administering a recipient cell transfer therapy. In some embodiments of the methods provided herein, the adaptive cell transfer therapy is the use of an engineered T cell receptor or a chimeric antigen receptor.

在本文提供的方法之一些實施例中，受試者患有傳染性疾病。在本文提供的方法之一些實施例中，傳染性疾病為細菌感染、病毒感染、寄生蟲感染或真菌感染。在本文提供的方法之一些實施例中，傳染性疾病為病毒感染。在本文提供的方法之一些實施例中，病毒感染為HIV。在本文提供的方法之一些實施例中，感染為由肝炎病毒的感染。In some embodiments of the methods provided herein, the subject has an infectious disease. In some embodiments of the methods provided herein, the infectious disease is a bacterial infection, a viral infection, a parasitic infection, or a fungal infection. In some embodiments of the methods provided herein, the infectious disease is a viral infection. In some embodiments of the methods provided herein, the viral infection is HIV. In some embodiments of the methods provided herein, the infection is an infection by a hepatitis virus.

在本文提供的方法之一些實施例中，受試者患有自體免疫疾病或過敏性疾病。In some embodiments of the methods provided herein, the subject has an autoimmune disease or an allergic disease.

在本文提供的方法之一些實施例中，組成物進一步包括一或多種消炎劑。在本文提供的方法之一些實施例中，消炎劑為NSAID。在本文提供的方法之一些實施例中，組成物可以一或多種劑量投與。In some embodiments of the methods provided herein, the composition further includes one or more anti-inflammatory agents. In some embodiments of the methods provided herein, the anti-inflammatory agent is an NSAID. In some embodiments of the methods provided herein, the composition may be administered in one or more doses.

在一個態樣中，本揭示內容提供包括判定本文提供的任何組成物之一或多種細菌物種是否存在於受試者之腸內的方法，其中若存在小於100%、小於90%、小於80%、小於70%、小於60%、小於50%、小於40%、小於30%、小於20%、小於10%之細菌物種，或不存在細菌物種，則將組成物投與至該受試者。In one aspect, the present disclosure provides a method comprising determining whether one or more of the bacterial species provided herein are present in the intestine of a subject, wherein if present, less than 100%, less than 90%, less than 80% , Less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10% of bacterial species, or no bacterial species are present, the composition is administered to the subject.

在本文提供的方法之一些實施例中，受試者經歷或將經歷癌症治療。In some embodiments of the methods provided herein, the subject undergoes or will undergo cancer treatment.

在一個態樣中，本揭示內容提供用於判定是否預期受試者對癌症治療積極反應的方法，其中該方法包括判定本文提供的任何組成物之一或多種細菌物種是否存在於受試者之腸內，其中若存在小於100%、小於90%、小於80%、小於70%、小於60%、小於50%、小於40%、小於30%、小於20%、小於10%之細菌物種，或不存在細菌物種，則不預期該受試者對癌症治療積極反應。In one aspect, the disclosure provides a method for determining whether a subject is expected to respond positively to cancer treatment, wherein the method includes determining whether one or more of the bacterial species provided herein are present in the subject. In the gut, if there are less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, In the absence of bacterial species, the subject is not expected to respond positively to cancer treatment.

在本文提供的方法之一些實施例中，癌症治療為癌症免疫療法治療。In some embodiments of the methods provided herein, the cancer treatment is a cancer immunotherapy treatment.

在一個態樣中，本揭示內容提供用於降低受試者的病毒感染風險之方法，其中該方法包括判定本文提供的任何組成物之一或多種細菌物種是否存在於受試者之腸內，其中若存在小於100%、小於90%、小於80%、小於70%、小於60%、小於50%、小於40%、小於30%、小於20%、小於10%之細菌物種，或不存在細菌物種，則將組成物投與至該受試者，進而降低該受試者的病毒感染風險。In one aspect, the present disclosure provides a method for reducing the risk of viral infection in a subject, wherein the method includes determining whether one or more of the bacterial species provided herein are present in the intestine of the subject, Among them, if there are less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, or no bacteria Species, the composition is administered to the subject, thereby reducing the risk of viral infection in the subject.

在本文提供的方法之一些實施例中，判定細菌物種中之一或多者之存在係藉由將受試者之糞便物測序來進行。在本文提供的方法之一些實施例中，判定細菌物種中之一或多者之存在係藉由將受試者之糞便物之16S rDNA序列測序來進行。In some embodiments of the methods provided herein, determining the presence of one or more of the bacterial species is performed by sequencing the subject's fecal matter. In some embodiments of the methods provided herein, determining the presence of one or more of the bacterial species is performed by sequencing the 16S rDNA sequence of the subject's fecal matter.

在一個態樣中，本揭示內容提供在腸道中誘導產生T細胞之CD8+ IFN-γ之活化的組成物及方法。In one aspect, the present disclosure provides compositions and methods for inducing activation of CD8 + IFN-γ producing T cells in the intestine.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下NCBI登錄號之序列具有至少95%同源性之16S rDNA序列：LN998073、KR822463、CP011531、NR_112945、NZ-ACWW00000000、AB331897、AB261128、NZ-CAEG00000000、AB470343、AB595134、HE974920、NR_112933、AB490801、NZ-ACWB00000000、AY608696、CR626927、AB247141、NR_112935、AB249652、NR_113076及AF139525。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。在本文提供的組成物之一些實施例中，該一或多種細菌菌株包含與本文提供的序列具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising 16S having at least 95% homology to a sequence of the following NCBI accession number rDNA sequence: LN998073, KR822463, CP011531, NR_112945, NZ-ACWW00000000, AB331897, AB261128, NZ-CAEG00000000, AB470343, AB595134, HE974920, NR_112933, AB490801, NZ-ACWB00000000, AY608696, CR626927, AB247141, NR_112935, AB249AF, 525_NR . In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains. In some embodiments of the compositions provided herein, the one or more bacterial strains comprise a 16S rDNA sequence having at least 96%, at least 97%, at least 98%, or at least 99% homology to the sequences provided herein.

在一個態樣中，本揭示內容提供誘導或活化產生CD8+IFNγ之T細胞的組成物，該組成物包含(i)自人類糞便收集的擁有對安比西林之抗性的一或多種純化細菌菌株，或(ii)(i)之培養上清液。在本文提供的組成物之一些實施例中，組成物包含(a)純化細菌混合物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株 糞考拉桿菌；LN998073， 潰瘍梭桿菌；KR822463， 多利擬桿菌；CP011531， 單形擬桿菌；NR_112945， 罕見小球菌屬4_3_54A2FAA；NZ-ACWW00000000， Paraprevotella xylaniphila；AB331897， 約氏副擬桿菌；AB261128， 別樣桿菌屬JC136；NZ-CAEG00000000， 戈登副擬桿菌；AB470343， 黏真桿菌；AB595134， 狄氏副擬桿菌；HE974920， 解纖維素擬桿菌；NR_112933， 克拉氏擬桿菌；AB490801， 厭氧棒狀菌屬3_2_56FAA；NZ-ACWB00000000， 塞爾氏擬桿菌；AY608696， 脆弱擬桿菌；CR626927， 單形擬桿菌；AB247141， 埃氏擬桿菌；NR_112935， 梭菌屬TM-40；AB249652， 古氏副擬桿菌；NR_113076，及 擬桿菌屬AR29；AF139525，或(b)一或多種細菌菌株，該等細菌菌株包含與選自由以下各項組成之群的物種之16S rRNA序列具有至少97%同源性之16S rRNA序列 糞考拉桿菌；LN998073， 潰瘍梭桿菌；KR822463， 多利擬桿菌；CP011531， 單形擬桿菌；NR_112945， 罕見小球菌屬4_3_54A2FAA；NZ-ACWW00000000， Paraprevotella xylaniphila；AB331897， 約氏副擬桿菌；AB261128， 別樣桿菌屬JC136；NZ-CAEG00000000， 戈登副擬桿菌；AB470343， 黏真桿菌；AB595134， 狄氏副擬桿菌；HE974920， 解纖維素擬桿菌；NR_112933， 克拉氏擬桿菌；AB490801， 厭氧棒狀菌屬3_2_56FAA；NZ-ACWB00000000， 塞爾氏擬桿菌；AY608696， 脆弱擬桿菌；CR626927， 單形擬桿菌；AB247141， 埃氏擬桿菌；NR_112935， 梭菌屬TM-40；AB249652， 古氏副擬桿菌；NR_113076，及 擬桿菌屬AR29；AF139525In one aspect, the present disclosure provides a composition that induces or activates CD8 + IFNγ-producing T cells, the composition comprising (i) one or more purified bacterial strains collected from human feces having resistance to ampicillin , Or (ii) (i) culture supernatant. In some embodiments of the composition provided herein, the composition comprises (a) a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of Koalabacterium faecalis, LN998073, Clostridium ulcerans; KR822463, Bacteroides dorisi; CP011531, Bacteroides spp .; NR_112945, Rare micrococcus 4_3_54A2FAA; NZ-ACWW00000000, Paraprevotella xylaniphila; AB331897, Parabola yojei; AB261128, Allobacterium JC136; NZ- CAEG00000000, B. gordonii; AB470343, Myxobacteria; AB595134, B. dickii; HE974920, B. cellulolyticus; NR_112933, B. kelasi; AB490801, Anaerobic corynebacterium 3_2_56FAA; NZ-ACWB00000000 , Bacteroides selenoides; AY608696, Bacteroides fragile; CR626927, Bacteroides morphogenes; AB247141, Bacteroides escherichia; NR_112935, Clostridium TM-40; AB249652, Pseudomonas archaea; NR_113076, and Bacteroides AR29; AF139525, or (b) one or more bacterial strains comprising and selected from the group consisting of The 16S rRNA sequence of the group of species has at least 97% homology to the 16S rRNA sequence of K. faecalis; LN998073, Clostridium ulcerans; KR822463, Bacteroides doulisi; CP011531, Bacteroides monomorphum; NR_112945, Rare micrococcus 4_3_54A2FAA NZ-ACWW00000000, Paraprevotella xylaniphila; AB331897, Pseudomonas yojei; AB261128, Pseudomonas genus JC136; NZ-CAEG00000000, Pseudomonas gordonii; AB470343, Pseudomonas myxobacteria; AB595134, Pseudomonas diescherii; HE974920, Cellulolytic Bacterium; NR_112933, Bacteroides clarkii; AB490801, Anaerobic corynebacterium 3_2_56FAA; NZ-ACWB00000000, Bacteroides selenoides; AY608696, Bacteroides fragile; CR626927, Bacteroides fabri; AB247141, Escherichia Bacteroides; NR_112935, Clostridium TM-40; AB249652, B. archaea; NR_113076, and Bacteroides AR29; AF139525

在本文提供的組成物之一些實施例中，組成物包含純化細菌混合物，該純化細菌混合物包含(a)選自由以下各項組成之群的物種之一或多種細菌菌株 糞考拉桿菌；LN998073， 潰瘍梭桿菌；KR822463， 多利擬桿菌；CP011531， 單形擬桿菌；NR_112945， 罕見小球菌屬4_3_54A2FAA；NZ-ACWW00000000， Paraprevotella xylaniphila；AB331897， 約氏副擬桿菌；AB261128， 別樣桿菌屬JC136；NZ-CAEG00000000， 戈登副擬桿菌；AB470343， 黏真桿菌；AB595134，及 狄氏副擬桿菌；HE974920；或(b)一或多種細菌菌株，該等細菌菌株包含屬由以下各項組成之群的物種之16S rRNA序列 糞考拉桿菌；LN998073， 潰瘍梭桿菌；KR822463， 多利擬桿菌；CP011531， 單形擬桿菌；NR_112945， 罕見小球菌屬4_3_54A2FAA；NZ-ACWW00000000， Paraprevotella xylaniphila；AB331897， 約氏副擬桿菌；AB261128， 別樣桿菌屬JC136；NZ-CAEG00000000， 戈登副擬桿菌；AB470343， 黏真桿菌；AB595134，及 狄氏副擬桿菌；HE974920。In some embodiments of the composition provided herein, the composition comprises a purified bacterial mixture comprising (a) one or more bacterial strains selected from the group consisting of Koalabacterium faecalis, LN998073, Clostridium ulcerans; KR822463, Bacteroides dorisi; CP011531, Bacteroides spp .; NR_112945, Rare micrococcus 4_3_54A2FAA; NZ-ACWW00000000, Paraprevotella xylaniphila; AB331897, Parabola yojei; AB261128, Allobacterium JC136; NZ- CAEG00000000, B. gordonii; AB470343, Myxobacteria; AB595134, and B. dickii; HE974920; or (b) one or more bacterial strains comprising species belonging to the group consisting of 16S rRNA sequence of Coccus faecalis; LN998073, Clostridium ulcerans; KR822463, Bacteroides ulcerans; CP011531, Bacteroides morphogenes; NR_112945, Rare micrococcus 4_3_54A2FAA; NZ-ACWW00000000, Paraprevotella xylaniphila; AB331897, Parabibacterium AB261128, Mycobacterium genus JC136; NZ-CAEG00000000, B. gordonii; A B470343, Myxobacteria; AB595134, and B. dickii; HE974920.

在本文提供的組成物之一些實施例中，產生CD8+ IFNγ之T細胞表現CD103或顆粒酶B。In some examples of the compositions provided herein, CD8 + IFNγ producing T cells exhibit CD103 or Granzyme B.

在本文提供的組成物之一些實施例中，組成物活化免疫系統。In some embodiments of the composition provided herein, the composition activates the immune system.

在一個態樣中，本揭示內容提供用於活化免疫系統之方法，該方法包含投與本文提供的組成物中之一或多者。In one aspect, the present disclosure provides a method for activating the immune system, the method comprising administering one or more of the compositions provided herein.

在一個態樣中，本揭示內容提供用於活化產生CD8+ IFNγ之T細胞之方法，該方法包含將本文提供的組成物中之一或多者投與至受試者。In one aspect, the present disclosure provides a method for activating CD8 + IFNγ producing T cells, the method comprising administering one or more of the compositions provided herein to a subject.

在一個態樣中，本揭示內容提供用於誘導腸內CD8+ T細胞之增殖及/或累積之方法，其包含向受試者投與本文提供的組成物中之任何一或多者，其中該投與導致在該受試者之腸內誘導CD8+ T細胞之增殖及/或累積。In one aspect, the present disclosure provides a method for inducing proliferation and / or accumulation of intestinal CD8 + T cells, comprising administering to a subject any one or more of the compositions provided herein, wherein the Administration results in induction of proliferation and / or accumulation of CD8 + T cells in the intestine of the subject.

在一個態樣中，本揭示內容提供用於輔助治療及/或預防癌症或病毒感染之方法，其包含向受試者投與本文提供的組成物中之任何一或多者，其中該投與預防、治療、輔助治療及/或預防癌症或病毒感染。In one aspect, the present disclosure provides a method for adjuvant treatment and / or prevention of a cancer or viral infection, comprising administering to a subject any one or more of the compositions provided herein, wherein the administering Prevention, treatment, adjuvant therapy and / or prevention of cancer or viral infection.

在一個態樣中，本揭示內容提供疫苗組成物，其誘導針對本文揭示的組成物中之任一者之細菌菌株的免疫反應。In one aspect, the disclosure provides a vaccine composition that induces an immune response against a bacterial strain of any of the compositions disclosed herein.

在一個態樣中，本揭示內容提供疫苗組成物，其含有來源於本文提供的組成物中之任一者之細菌物種的成分及/或代謝物的抗原。In one aspect, the present disclosure provides a vaccine composition comprising antigens derived from components and / or metabolites of a bacterial species of any of the compositions provided herein.

在一個態樣中，本揭示內容提供用於誘導受試者之免疫反應的方法，其包含向該受試者投與本文提供的任何疫苗，其中該投與導致該受試者之免疫反應之誘導。In one aspect, the present disclosure provides a method for inducing an immune response in a subject, comprising administering to the subject any vaccine provided herein, wherein the administering results in an immune response in the subject. Induce.

在一個態樣中，本揭示內容提供免疫抑制組成物。In one aspect, the present disclosure provides an immunosuppressive composition.

在一個態樣中，本揭示內容提供包含組成物，其包含擁有針對本文的組成物中之任一者之細菌物種的抗菌活性之化學物質，或結合自本文提供的組成物中之任一者之細菌物種分泌的生理學活性物質之化學物質。In one aspect, the present disclosure provides a composition comprising a chemical substance having an antibacterial activity against a bacterial species of any of the compositions herein, or incorporated in any of the compositions provided herein A chemical substance that is a physiologically active substance secreted by a bacterial species.

在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者體內產生CD8+及IFNγ之T細胞之活性的抑制。In some embodiments of the compositions provided herein, administering the composition to a subject results in inhibition of the activity of T cells that produce CD8 + and IFNγ in the subject.

在一個態樣中，本揭示內容提供用於抑制受試者體內的產生CD8+及IFNγ之T細胞之方法，該方法包含將本文提供的組成物中之一或多者投與至該受試者。In one aspect, the present disclosure provides a method for inhibiting CD8 + and IFNγ producing T cells in a subject, the method comprising administering to the subject one or more of the compositions provided herein .

在一個態樣中，本揭示內容提供用於預防、治療或改良因受試者之產生CD8+及IFNγ之T細胞的過活化而引起的疾病之方法，該方法包含向該受試者投與本文提供的組成物中之任何一或多者至該受試者。In one aspect, the present disclosure provides a method for preventing, treating, or ameliorating a disease caused by a subject's over-activation of CD8 + and IFNγ-producing T cells, the method comprising administering to the subject Any one or more of the provided compositions are to the subject.

在一個態樣中，本揭示內容提供來源於本文揭示的細菌菌株之物質。在一個態樣中，本揭示內容提供來源於本文提供的組成物中之任一者之細菌物種的生理學活性物質。在一個態樣中，本揭示內容提供本文提供的組成物中之任一者之細菌物種中任一者的細菌特異性抗原。In one aspect, the disclosure provides material derived from a bacterial strain disclosed herein. In one aspect, the disclosure provides a physiologically active substance derived from a bacterial species of any of the compositions provided herein. In one aspect, the disclosure provides a bacterial-specific antigen of any of the bacterial species of any of the compositions provided herein.

在一個態樣中，本揭示內容提供特異地結合本文提供的組成物中之任一者之細菌物種的抗體。In one aspect, the disclosure provides antibodies that specifically bind to a bacterial species of any of the compositions provided herein.

在一個態樣中，本揭示內容提供在本文提供的組成物之細菌物種中之任一者內含有的細菌特異性核苷酸序列。In one aspect, the disclosure provides a bacterial-specific nucleotide sequence contained within any of the bacterial species of the compositions provided herein.

在一個態樣中，本揭示內容提供動物模型及測試套組。In one aspect, the present disclosure provides animal models and test kits.

在一個態樣中，本揭示內容提供包含非人類哺乳動物之動物模型，其中該非人類哺乳動物之腸道已利用本文提供的組成物中之任一者之細菌物種接種。在本文提供的動物模型之一些實施例中，非人類哺乳動物患有因產生CD8+ IFNγ之T細胞之不規則性引起的疾病。In one aspect, the present disclosure provides an animal model comprising a non-human mammal, wherein the non-human mammal's intestine has been inoculated with a bacterial species of any of the compositions provided herein. In some embodiments of the animal models provided herein, a non-human mammal has a disease caused by irregularities in T cells that produce CD8 + IFNγ.

在一個態樣中，本揭示內容提供用於評估產生CD8+ IFNγ之T細胞之活化的套組，該套組包含：腸上皮細胞、末梢血液單核細胞及本文提供的組成物中之任一者之細菌物種。In one aspect, the present disclosure provides a set for assessing the activation of CD8 + IFNγ-producing T cells, the set comprising: intestinal epithelial cells, peripheral blood mononuclear cells, and any of the compositions provided herein Bacterial species.

在一個態樣中，本揭示內容提供偵測人類腸道內產生CD8+ IFNγ之T細胞之方法。在一個態樣中，本揭示內容提供用於評估產生CD8+ IFNγ之T細胞之活化的套組。在一些實施例中，套組包含腸上皮細胞、末梢單核細胞及本文描述的任何組成物之細菌物種。In one aspect, the present disclosure provides a method for detecting CD8 + IFNγ producing T cells in the human intestine. In one aspect, the present disclosure provides a kit for assessing the activation of CD8 + IFNγ producing T cells. In some embodiments, the kit comprises intestinal epithelial cells, peripheral monocytes, and bacterial species of any composition described herein.

在一個態樣中，本揭示內容提供用於篩選細菌或來源於人類腸細菌之生理學活性物質的方法，其中該物質誘導該腸道內產生CD8+ IFNγ之T細胞之活化，該方法包含(i)使非人類無菌動物攝取來源於人類腸細菌之生理學活性物質或細菌，(ii)偵測該非人類無菌動物之該腸道內產生CD8+ IFNγ之T細胞之數量或活性，其中若偵測到產生CD8+ IFNγ之T細胞之活化，則該生理學活性物質係識別為可活化產生CD8+ IFNγ之T細胞之物質。In one aspect, the present disclosure provides a method for screening a bacterium or a physiologically active substance derived from a human intestinal bacterium, wherein the substance induces activation of CD8 + IFNγ-producing T cells in the intestine, the method comprising (i ) Make a non-human sterile animal ingest a physiologically active substance or bacteria derived from a human intestinal bacterium, (ii) detect the number or activity of CD8 + IFNγ-producing T cells in the intestine of the non-human sterile animal, where if detected The activation of CD8 + IFNγ-producing T cells is then recognized as a substance that can activate CD8 + IFNγ-producing T cells.

在一個態樣中，本揭示內容提供用於篩選細菌或來源於人類腸細菌之生理學活性物質的方法，其中該物質誘導該腸道內產生CD8+ IFNγ之T細胞之增殖或活化，該方法包含(i)將來源於人類腸細菌之生理學活性物質或細菌添加至包含腸上皮細胞及末梢血液單核細胞之系統中之腸上皮細胞；(ii)偵測該系統內產生CD8+ IFNγ之T細胞之數量或活性，其中若偵測到產生CD8+ IFNγ之T細胞之活化，則該生理學活性物質係識別為可活化產生CD8+ IFNγ之T細胞之物質。In one aspect, the present disclosure provides a method for screening bacteria or a physiologically active substance derived from human intestinal bacteria, wherein the substance induces proliferation or activation of CD8 + IFNγ-producing T cells in the intestine, the method comprising (i) adding physiologically active substances or bacteria derived from human intestinal bacteria to intestinal epithelial cells in a system containing intestinal epithelial cells and peripheral blood mononuclear cells; (ii) detecting T cells that produce CD8 + IFNγ in the system The amount or activity, if the activation of CD8 + IFNγ-producing T cells is detected, the physiologically active substance is identified as a substance that can activate CD8 + IFNγ-producing T cells.

在一個態樣中，本揭示內容提供用於篩選誘導腸道內產生CD8+ IFNγ之T細胞之活化的物質之方法，其包含(i)將來源於細菌或在本文提供的組成物中含有的細菌之生理學活性物質添加至含有腸上皮細胞及末梢血液單核細胞之系統，(ii)添加測試物質，(iii)偵測該系統內產生CD8+ IFNγ之T細胞之數量或活性，其中若在上文步驟中偵測到的產生CD8+ IFNγ之T細胞之數量或活性增加，則該測試物質係識別為誘導產生CD8+ IFNγ之T細胞之活化的物質。In one aspect, the present disclosure provides a method for screening a substance that induces the activation of CD8 + IFNγ-producing T cells in the intestine, comprising (i) a bacterium that will be derived from a bacterium or contained in a composition provided herein The physiologically active substance is added to a system containing intestinal epithelial cells and peripheral blood mononuclear cells, (ii) a test substance is added, and (iii) the number or activity of T cells that produce CD8 + IFNγ in the system is detected. An increase in the number or activity of CD8 + IFNγ-producing T cells detected in this step, the test substance is identified as a substance that induces the activation of CD8 + IFNγ-producing T cells.

在一個態樣中，本揭示內容提供用於篩選誘導腸道內產生CD8+ IFNγ之T細胞之活化的物質之方法，其包含(i)用於篩選本文提供的非人類動物之方法，(ii)偵測該非人類動物之該腸道內產生CD8+ IFNγ之T細胞之數量或活性，其中若在上文步驟中偵測到的產生CD8+ IFNγ之T細胞之數量或活性增加，則該測試物質係識別為誘導產生CD8+ IFNγ之T細胞之活化的物質。In one aspect, the present disclosure provides a method for screening a substance that induces the activation of CD8 + IFNγ-producing T cells in the gut, comprising (i) a method for screening a non-human animal provided herein, (ii) Detecting the number or activity of CD8 + IFNγ-producing T cells in the intestine of the non-human animal, wherein if the number or activity of CD8 + IFNγ-producing T cells detected in the above steps is increased, the test substance is recognized It is a substance that induces the activation of CD8 + IFNγ-producing T cells.

在一個態樣中，本揭示內容提供用於刺激免疫性之組成物，該組成物包含作為活性成分之人類腸細菌或來源於藉由本文提供的篩選方法獲得的細菌之生理學活性物質。在本文提供的組成物之一些實施例中，組成物誘導產生CD8+ IFNγ之T細胞之活化。In one aspect, the present disclosure provides a composition for stimulating immunity, the composition comprising a human intestinal bacterium as an active ingredient or a physiologically active substance derived from a bacterium obtained by the screening method provided herein. In some embodiments of the compositions provided herein, the composition induces activation of T cells that produce CD8 + IFNγ.

在一個態樣中，本揭示內容提供疫苗組成物，其包含作為活性成分之藉由本文提供的任何篩選方法獲得的人類腸細菌或對該細菌有特異性之抗原。In one aspect, the present disclosure provides a vaccine composition comprising, as an active ingredient, a human intestinal bacterium obtained by any of the screening methods provided herein or an antigen specific to the bacterium.

在一個態樣中，本揭示內容提供用於篩選物質之方法，該物質具有誘導或惡化由產生CD8+ IFNγ之T細胞所引起的疾病之活性，該方法包含(i)使測試物質由本文提供的非人類動物攝取，(ii)偵測由該非人類動物體內產生CD8+ IFNγ之T細胞所引起的疾病相關破壞程度，其中在上文步驟中偵測到的損害程度相較於不添加化合物或安慰劑時增加時，該測試物質係識別為誘導由產生CD8+ IFNγ之T細胞所引起的疾病之物質。In one aspect, the present disclosure provides a method for screening a substance having an activity that induces or aggravates a disease caused by CD8 + IFNγ producing T cells, the method comprising (i) causing a test substance to be provided by Uptake by non-human animals, (ii) Detecting the degree of disease-related damage caused by CD8 + IFNγ-producing T cells in the non-human animal, wherein the degree of damage detected in the above step is compared to the absence of compound or placebo When it increases, the test substance is recognized as a substance that induces a disease caused by CD8 + IFNγ producing T cells.

在一個態樣中，本揭示內容提供用於誘導或惡化由產生CD8+ IFNγ之T細胞所引起的疾病之組成物，其中該組成物包含作為活性成分之藉由本文提供的篩選方法中之任一者獲得的物質。In one aspect, the present disclosure provides a composition for inducing or exacerbating a disease caused by CD8 + IFNγ producing T cells, wherein the composition comprises, as an active ingredient, any of the screening methods provided herein Obtained by the person.

在一個態樣中，本揭示內容提供包含經處理人類糞便樣本之組成物，其中該經處理人類糞便樣本係藉由使人類糞便樣本與安比西林接觸來獲得，且其中該經處理人類糞便樣本誘導CD8+ T細胞之增殖及/或累積。在一些實施例中，本揭示內容提供治療受試者之疾病之方法，該方法包含以治療該受試者之該疾病的有效量向該受試者投與本文提供的組成物中之任一者。在本文提供的方法之一些實施例中，疾病為癌症或感染(例如，病毒感染)。In one aspect, the present disclosure provides a composition comprising a processed human stool sample, wherein the processed human stool sample is obtained by contacting a human stool sample with ampicillin, and wherein the processed human stool sample induces CD8 + T cell proliferation and / or accumulation. In some embodiments, the present disclosure provides a method of treating a disease in a subject, the method comprising administering to the subject any of the compositions provided herein in an effective amount to treat the disease in the subject. By. In some embodiments of the methods provided herein, the disease is cancer or an infection (eg, a viral infection).

在一個態樣中，本揭示內容提供包含以下步驟之方法：在無菌小鼠中接種人類糞便樣本，及判定該人類糞便樣本是否誘導CD8+ T細胞之增殖及/或累積。In one aspect, the present disclosure provides a method comprising the steps of: inoculating a human stool sample in a sterile mouse, and determining whether the human stool sample induces the proliferation and / or accumulation of CD8 + T cells.

在一個態樣中，本揭示內容提供用於判定人類糞便樣本是否誘導CD8+ T細胞之增殖及/或累積之方法，其包含利用人類糞便樣本接種無菌小鼠，且判定該人類糞便樣本是否誘導CD8+ T細胞之增殖及/或累積。在一個態樣中，本揭示內容提供用於識別人類糞便供體之方法，其包含利用人類糞便樣本接種無菌小鼠，及判定該人類糞便樣本是否誘導CD8+ T細胞之增殖及/或累積，其中若該糞便樣本誘導CD8+ T細胞之增殖及/或累積，則該人類受試者係識別為人類糞便供體。In one aspect, the present disclosure provides a method for determining whether a human stool sample induces the proliferation and / or accumulation of CD8 + T cells, which comprises inoculating a sterile mouse with a human stool sample, and determining whether the human stool sample induces CD8 + T cell proliferation and / or accumulation. In one aspect, the present disclosure provides a method for identifying a human fecal donor, comprising inoculating a sterile mouse with a human fecal sample, and determining whether the human fecal sample induces the proliferation and / or accumulation of CD8 + T cells, wherein If the stool sample induces the proliferation and / or accumulation of CD8 + T cells, the human subject is identified as a human stool donor.

在一個態樣中，本揭示內容提供用於分析受試者之淋巴細胞中之標誌物的表現位準之方法，其包含分析該標誌物之該表現位準，其中該標誌物係藉由向該受試者投與本文描述的任何組成物來誘導，其中該標誌物為CD44、gp70 MC38肽(KSPWFTTL；(SEQ ID NO:53))特異性TCR、腫瘤抗原源配位體特異性TCR、CD8、IFNγ及/或GzmB。In one aspect, the present disclosure provides a method for analyzing a performance level of a marker in a subject's lymphocytes, comprising analyzing the performance level of the marker, wherein the marker is The subject is induced by administering any composition described herein, wherein the marker is CD44, gp70 MC38 peptide (KSPWFTTL; (SEQ ID NO: 53)) specific TCR, tumor antigen source ligand specific TCR, CD8, IFNγ and / or GzmB.

在一個態樣中，本揭示內容提供用於分析在誘導之後受試者之淋巴細胞中之標誌物的表現位準的套組，其中該標誌物係藉由向該受試者投與本文描述的任何組成物來誘導，其中該標誌物為CD44、gp70 MC38肽(KSPWFTTL；(SEQ ID NO:53))特異性TCR、腫瘤抗原源配位體特異性TCR、CD8、IFNγ及/或GzmB。In one aspect, the present disclosure provides a set for analyzing the performance level of a marker in a subject ' s lymphocytes after induction, wherein the marker is by administering to the subject described herein Induced by any composition, wherein the marker is CD44, gp70 MC38 peptide (KSPWFTTL; (SEQ ID NO: 53)) specific TCR, tumor antigen-derived ligand specific TCR, CD8, IFNγ and / or GzmB.

在一個態樣中，本揭示內容提供用於篩選細菌或來源於人類腸細菌之生理學活性物質之方法，該方法包含允許帶腫瘤非人類動物攝取來源於人類腸細菌或細菌之生理學活性物質，偵測自該帶腫瘤非人類動物分離的淋巴細胞中之標誌物之表現，其中若偵測到該標誌物之表現位準的增加，則該生理學活性物質係識別為用於腫瘤之免疫刺激劑；且其中該標誌物為CD44、gp70 MC38肽(KSPWFTTL；(SEQ ID NO:53))特異性TCR、腫瘤抗原源配位體特異性TCR、CD8、IFNγ及/或GzmB。In one aspect, the present disclosure provides a method for screening a bacterium or a physiologically active substance derived from a human intestinal bacterium, the method comprising allowing a tumor-bearing non-human animal to ingest a physiologically active substance derived from a human intestinal bacterium or bacteria To detect the expression of a marker in a lymphocyte isolated from a non-human animal with a tumor, and if an increase in the expression level of the marker is detected, the physiologically active substance is identified as being used for tumor immunity A stimulant; and wherein the marker is CD44, gp70 MC38 peptide (KSPWFTTL; (SEQ ID NO: 53)) specific TCR, tumor antigen source ligand specific TCR, CD8, IFNγ and / or GzmB.

在一個態樣中，本揭示內容提供用於利用免疫查核點抑制劑之腫瘤療法的伴隨式診斷方法，該方法包含分析在藉由具有或不具有該免疫查核點抑制劑之共同投與的情況下向該受試者投與本文描述的任何組成物進行誘導之前及之後淋巴細胞中之標誌物之表現位準，其中若該受試者之該等淋巴細胞中之該標誌物的該等表現位準相較於在向該受試者投與該組成物，共同投與該抑制劑及本文描述的任何組成物之前該受試者之該等淋巴細胞中之該等表現位準增加達至少10%、至少20%、至少30%至少40%、至少50%、至少100%或至少200%，則該療法繼續，其中若該受試者之該等淋巴細胞中之該等表現位準相較於該受試者之該等淋巴細胞中之該等表現位準不增加，則中斷該抑制劑及本文描述的任何組成物之共同投與，或在重複將本文描述的任何組成物投與至該受試者之後重新分析。In one aspect, the present disclosure provides a companion diagnostic method for oncology therapy using an immune checkpoint inhibitor, the method comprising analyzing the situation of co-administration with or without the immune checkpoint inhibitor The subject is administered the composition described herein with any of the compositions described herein before and after induction of the markers in the lymphocytes, where the performance of the markers in the lymphocytes of the subject The level of expression in the lymphocytes of the subject is increased by at least at least as compared to the composition before the composition is co-administered with the inhibitor and any composition described herein. 10%, at least 20%, at least 30% at least 40%, at least 50%, at least 100%, or at least 200%, the therapy continues, where the performance levels in the lymphocytes of the subject are in phase No increase in the expression levels in the lymphocytes of the subject, discontinue co-administration of the inhibitor and any composition described herein, or repeat administration of any composition described herein To the subject after Analysis.

在一些實施例中，該方法進一步包含利用結合至腫瘤抗原源配位體特異性TCR之特異性抗體或結合至腫瘤抗原源配位體特異性TCR之MHC單體集合體分析淋巴細胞中之腫瘤抗原源配位體特異性TCR之表現位準。在一些實施例中，該方法係用於利用免疫查核點抑制劑之腫瘤療法，其中該免疫查核點抑制劑為PD-1抑制劑、PD-L1抑制劑或CTLA-4抑制劑。在一些實施例中，該方法進一步包含評定受試者之T細胞中之PD-1表現。在一些實施例中，該方法進一步包含評定受試者之癌細胞中之PD-L1表現。在一些實施例中，該方法進一步包含評定受試者之T細胞中之CTLA-4表現。In some embodiments, the method further comprises analyzing tumors in lymphocytes using specific antibodies that bind to tumor antigen-derived ligand-specific TCRs or MHC monomer assemblies that bind to tumor antigen-derived ligand-specific TCRs. Performance level of antigen-derived ligand-specific TCR. In some embodiments, the method is for tumor therapy using an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor. In some embodiments, the method further comprises assessing PD-1 performance in the T cells of the subject. In some embodiments, the method further comprises assessing PD-L1 performance in the subject's cancer cells. In some embodiments, the method further comprises assessing CTLA-4 performance in the T cells of the subject.

在一個態樣中，本揭示內容提供用於執行伴隨式診斷方法之套組，其中該套組包含用於監視淋巴細胞中之標誌物之表現位準的一或多種分子，其中該標誌物為CD44、gp70 MC38肽(KSPWFTTL；(SEQ ID NO:53))特異性TCR、腫瘤抗原源配位體特異性TCR、CD8、IFNγ及/或GzmB。In one aspect, the present disclosure provides a set for performing a companion diagnostic method, wherein the set includes one or more molecules for monitoring the level of performance of a marker in a lymphocyte, wherein the marker is CD44, gp70 MC38 peptide (KSPWFTTL; (SEQ ID NO: 53)) specific TCR, tumor antigen-derived ligand specific TCR, CD8, IFNγ and / or GzmB.

在一個態樣中，本揭示內容提供用於利用脾細胞中之IFNγ產生程度來評估免疫活化之方法，該方法包含向受試者投與本文描述的任何組成物。In one aspect, the present disclosure provides a method for assessing immune activation using the extent of IFNγ production in splenocytes, the method comprising administering to a subject any composition described herein.

在一個態樣中，本揭示內容提供用於利用脾細胞中之IFNγ產生程度來評估免疫活化之套組，其包含一或多種IFNγ標誌物分子及本文描述的任何組成物之一或多種細菌物種。In one aspect, the present disclosure provides a kit for assessing immune activation using the extent of IFNγ production in spleen cells, comprising one or more IFNγ marker molecules and one or more bacterial species of any of the compositions described herein .

在一個態樣中，本揭示內容提供用於識別用於腫瘤之免疫刺激劑的方法，該方法包含篩選人類腸細菌或來源於人類腸細菌之生理學活性物質，該方法包含(i)使帶腫瘤非人類動物攝取該人類腸細菌或來源於該人類腸細菌之該生理學活性物質，及(ii)偵測自該帶腫瘤非人類動物分離的脾細胞中之IFNγ，其中若偵測到IFNγ之誘導，則該人類腸細菌或生理學活性物質係識別為用於該腫瘤之免疫刺激劑。In one aspect, the present disclosure provides a method for identifying an immunostimulant for a tumor, the method comprising screening a human intestinal bacterium or a physiologically active substance derived from a human intestinal bacterium, the method comprising (i) The tumor non-human animal ingests the human intestinal bacteria or the physiologically active substance derived from the human intestinal bacteria, and (ii) detects IFNγ in splenocytes isolated from the tumor-free non-human animal. Induction, the human intestinal bacteria or physiologically active substance is recognized as an immunostimulant for the tumor.

在一個態樣中，本揭示內容提供用於利用免疫查核點抑制劑之腫瘤療法的伴隨式診斷方法，該方法包含在藉由具有或不具有該抑制劑之共同投與的情況下向該受試者投與本文描述的任何組成物進行誘導之前及之後利用脾細胞中之IFNγ產生程度來評估免疫活化，其中若該受試者之該等脾細胞中之IFNγ產生程度相較於在該組成物之投與之前該受試者之該等脾細胞中之IFNγ產生程度增加達至少10%、至少20%、至少30%、至少40%、至少50%、至少100%或至少200%，則該抑制劑及本文描述的任何組成物向該受試者之共同投與繼續，其中若該受試者之該等脾細胞中之IFNγ產生程度不增加，則中斷該抑制劑及本文描述的任何組成物之共同投與，或在重複將本文描述的任何組成物投與至受試者之後重新分析。In one aspect, the present disclosure provides a companion diagnostic method for tumor therapy using an immune checkpoint inhibitor, the method comprising providing to the subject with co-administration with or without the inhibitor. The subject evaluates immune activation using the level of IFNγ production in the splenocytes before and after administration of any of the compositions described herein, wherein if the level of IFNγ production in the spleen cells of the subject is greater than that in the composition Before the administration of the substance, the degree of IFNγ production in the spleen cells of the subject has increased by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 100%, or at least 200%, then The co-administration of the inhibitor and any composition described herein to the subject continues, wherein if the subject does not increase the level of IFNγ production in the spleen cells, the inhibitor and any Co-administration of the composition, or reanalysis after repeated administration of any composition described herein to a subject.

在一些實施例中，該方法進一步包含利用特異性抗體或MHC單體集合體分析脾細胞中之療法標靶之腫瘤抗原的表現位準。在一些實施例中，該方法係用於利用免疫查核點抑制劑之腫瘤療法，其中該腫瘤抑制劑為PD-1抑制劑、PD-L1抑制劑或CTLA-4抑制劑。在一些實施例中，該方法進一步包含評定受試者之T細胞中之PD-1表現。在一些實施例中，該方法進一步包含評定受試者之癌細胞中之PD-L1表現。在一些實施例中，該方法進一步包含評定受試者之T細胞中之CTLA-4表現。In some embodiments, the method further comprises analyzing the performance level of the tumor antigen of the therapeutic target in the splenocytes using a specific antibody or MHC monomer assembly. In some embodiments, the method is for a tumor therapy using an immune checkpoint inhibitor, wherein the tumor inhibitor is a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor. In some embodiments, the method further comprises assessing PD-1 performance in the T cells of the subject. In some embodiments, the method further comprises assessing PD-L1 performance in the subject's cancer cells. In some embodiments, the method further comprises assessing CTLA-4 performance in the T cells of the subject.

在一個態樣中，本揭示內容提供用於進行本文描述的伴隨式診斷方法之套組，其包含一或多種IFNγ標誌物分子。In one aspect, the present disclosure provides a kit for performing the companion diagnostic methods described herein, which comprises one or more IFNγ marker molecules.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、梭桿菌屬、多利擬桿菌、細菌IARFR67、瘤胃菌科細菌、Paraprevotella xylaniphila、約氏副擬桿菌、擬桿菌屬、戈登副擬桿菌、黏真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Fusobacterium, Dolly Bacteroides, bacteria IARFR67, bacteria of the rumenaceae family, Paraprevotella xylaniphila, Bacteroides yojei, Bacteroides, B. gordonii, Pseudomonas myxobacteria, B. dickensii, B. cellulolyticus, B. kela , Anaerobic Corynebacterium, Bacteroides selenoides, Bacteroides fragile, Bacteroides morphogenes, Bacteroides escherichia, Clostridium, Pseudomonas archaea, Bacteroides, Trichomonas bacteria HGA0140, Hungatella hathewayi, Clostridium lavas, rumenococcus and harmless Clostridium. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 , At least 23, at least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、梭桿菌屬、多利擬桿菌、細菌IARFR67、瘤胃菌科細菌、Paraprevotella xylaniphila、約氏副擬桿菌、擬桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Fusobacterium, Dolly Bacteroides, bacteria IARFR67, bacteria of the rumenaceae family, Paraprevotella xylaniphila, Bacteroides yojei, Bacteroides, B. gordonii, Eubacillus myxoides, B. dickensii, B. cellulolyticus, B. cladii , Anaerobic Corynebacterium, Bacteroides selenoides, Bacteroides fragile, Bacteroides morphogenes, Bacteroides escherichia, Clostridium, B. archaea and Bacteroides In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、梭桿菌屬、多利擬桿菌、細菌IARFR67、瘤胃菌科細菌、Paraprevotella xylaniphila、約氏副擬桿菌、擬桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Fusobacterium, Dolly Bacteroides, bacteria IARFR67, bacteria of the rumenaceae family, Paraprevotella xylaniphila, Bacteroides yojei, Bacteroides, Bacteroides gordonii, Eumycobacteria mycoides, and B. dickensii. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、梭桿菌屬、瘤胃菌科細菌及黏液真桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Fusobacterium, rumen Mycobacteria and Eumycobacterium mucus. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：多利擬桿菌、細菌IARFR67、Paraprevotella xylaniphila、約氏副擬桿菌、擬桿菌屬、戈登副擬桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Bacteroides dorylii, bacteria IARFR67, Paraprevotella xylaniphila, J. yojei, B. genus, B. gordonii, and B. dickii. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains.

本發明之每一限制可涵蓋本發明之各種實施例。因此預期本發明之每一限制涉及任一要素或要素之組合可包括在本發明之每一態樣中。本發明之應用不限於以下描述中闡述或圖式中說明的構造細節及組件佈置。本發明能夠有其他實施例且以各種方式實踐或進行。Each limitation of the invention may cover various embodiments of the invention. It is therefore contemplated that each limitation of the invention may involve any one element or combination of elements that may be included in each aspect of the invention. The invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced or carried out in various ways.

本文提供的用於誘導及/或增殖CD8+ T細胞之組成物及方法，以及用於治療包括傳染性疾病及癌症的疾病及病狀之方法，該等疾病及病狀可經由誘導及/或增殖CD8+ T細胞來治療。Compositions and methods for inducing and / or proliferating CD8 + T cells provided herein, and methods for treating diseases and conditions including infectious diseases and cancer, which can be induced and / or proliferated CD8 + T cells.

在一個態樣中，本揭示內容提供包含一或多種具有獨特生物學性質之細菌菌株的組成物。在一個態樣中，本文揭示的細菌菌株之組成物(亦稱為細菌組成物)可誘導CD8+ T細胞之增殖及/或累積。在一個態樣中，本文揭示的細菌菌株之組成物可誘導CD8+ T細胞之增殖及/或累積。In one aspect, the disclosure provides a composition comprising one or more bacterial strains having unique biological properties. In one aspect, the composition of a bacterial strain (also referred to as a bacterial composition) disclosed herein can induce the proliferation and / or accumulation of CD8 + T cells. In one aspect, the composition of the bacterial strains disclosed herein can induce the proliferation and / or accumulation of CD8 + T cells.

在一個態樣中，本文揭示的組成物之細菌可藉由其16S rRNA (或16S rDNA)核酸序列識別。一般而言，細菌係基於其16S rRNA核酸序列分類為屬於特定種及/或屬。諸如來源於微生物群之細菌的細菌亦可與其他緊密相關菌株及物種分類成系統集群。(參見，例如，Rajilic-Stojanovic，M.及de Vos，W.M. (2014). The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol Rev 38，996-1047)。用於基於特定細菌物種之16S rRNA (或16S rDNA)核酸序列來判定該等特定細菌物種之身份的方法在此項技術中為熟知的(參見，例如，Jumpstart Consortium Human Microbiome Project Data Generation Working，G. (2012). Evaluation of 16S rDNA-based community profiling for human microbiome research. PLoS One 7，e39315)。In one aspect, the bacteria of the composition disclosed herein can be identified by their 16S rRNA (or 16S rDNA) nucleic acid sequence. Generally, bacteria are classified as belonging to a specific species and / or genus based on their 16S rRNA nucleic acid sequence. Bacteria such as bacteria derived from the microbiome can also be grouped into clusters with other closely related strains and species. (See, for example, Rajilic-Stojanovic, M. and de Vos, W.M. (2014). The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol Rev 38, 996-1047). Methods for determining the identity of specific bacterial species based on their 16S rRNA (or 16S rDNA) nucleic acid sequences are well known in the art (see, for example, Jumpstart Consortium Human Microbiome Project Data Generation Working, G (2012). Evaluation of 16S rDNA-based community profiling for human microbiome research. PLoS One 7, e39315).

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17.SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 , At least 23, at least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17.SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 , At least 23, at least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO : 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO : 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20及SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17. SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 and SEQ ID NO: 21. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20及SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17. SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 and SEQ ID NO: 21. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20及SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20及SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63 or SEQ ID NO: 64. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61 , SEQ ID NO: 62, SEQ ID NO: 63 or SEQ ID NO: 64. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least Ten, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least Ten, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 , SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19 , SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the disclosure provides a composition comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to the following: SEQ ID NO: 12, SEQ ID NO : 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21 . In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 bacterial strains.

在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to the following: SEQ ID NO: 12, SEQ ID NO : 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21 . In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 bacterial strains.

在一個態樣中，本揭示內容提供包含兩種或更多種細菌菌株之組成物，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the disclosure provides a composition comprising two or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to the following: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含兩種或更多種細菌菌株之組成物，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the disclosure provides a composition comprising two or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity with the following: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 , At least 23, at least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 , At least 23, at least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO : 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO : 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34 , SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least Ten, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least Ten, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41，SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45 , SEQ ID NO: 46 or SEQ ID NO: 47. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31, or SEQ ID NO: 36. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31, or SEQ ID NO: 36. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31 or SEQ ID NO: 36. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31 or SEQ ID NO: 36. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% homology to: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity to: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

在一個態樣中，本揭示內容提供包含細菌菌株之組成物，該細菌菌株包含具有選自由SEQ ID NO:1-26組成之群的核酸序列之16S rDNA序列。在一個態樣中，本揭示內容提供包含作為活性成分之細菌菌株之組成物，該細菌菌株包含具有選自由SEQ ID NO:1-26組成之群的核酸序列之16S rDNA序列。應瞭解，對本文提供的所有組成物而言，在一些實施例中，該或該等細菌菌株為組成物之活性成分。In one aspect, the present disclosure provides a composition comprising a bacterial strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26. In one aspect, the present disclosure provides a composition comprising a bacterial strain as an active ingredient, the bacterial strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26. It should be understood that for all the compositions provided herein, in some embodiments, the bacterial strain or strains are the active ingredients of the composition.

在一個態樣中，本揭示內容提供包含細菌菌株之組成物，該細菌菌株包含具有選自由SEQ ID NO:1-21組成之群的核酸序列之16S rDNA序列。在一個態樣中，本揭示內容提供包含作為活性成分之細菌菌株之組成物，該細菌菌株包含具有選自由SEQ ID NO:1-21組成之群的核酸序列之16S rDNA序列。In one aspect, the present disclosure provides a composition comprising a bacterial strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-21. In one aspect, the present disclosure provides a composition comprising a bacterial strain as an active ingredient, the bacterial strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-21.

在一個態樣中，本揭示內容提供包含細菌菌株之組成物，該細菌菌株包含具有選自由SEQ ID NO:1-11組成之群的核酸序列之16S rDNA序列。在一個態樣中，本揭示內容提供包含作為活性成分之細菌菌株之組成物，該細菌菌株包含具有選自由SEQ ID NO:1-11組成之群的核酸序列之16S rDNA序列。In one aspect, the present disclosure provides a composition comprising a bacterial strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-11. In one aspect, the present disclosure provides a composition comprising a bacterial strain as an active ingredient, the bacterial strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-11.

在一個態樣中，本揭示內容提供包含細菌菌株之組成物，該細菌菌株包含具有選自由SEQ ID NO:54-64組成之群的核酸序列之16S rDNA序列。在一個態樣中，本揭示內容提供包含作為活性成分之細菌菌株之組成物，該細菌菌株包含具有選自由SEQ ID NO:54-64組成之群的核酸序列之16S rDNA序列。In one aspect, the present disclosure provides a composition comprising a bacterial strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 54-64. In one aspect, the present disclosure provides a composition comprising a bacterial strain as an active ingredient, the bacterial strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 54-64.

應瞭解，對本文提供的所有組成物而言，在一些實施例中，細菌菌株為純化的。因此，例如，本揭示內容提供純化細菌菌株，其包含具有選自由SEQ ID NO:1-26組成之群的核酸序列之16S rDNA序列。另外，例如，本揭示內容提供包含純化細菌菌株之組成物，該等純化細菌菌株包含具有選自由SEQ ID NO:1-26組成之群的核酸序列之16S rDNA序列。本文揭示的細菌菌株原始地可已自一或多個人類個體之微生物群獲得並純化，或自不同於人類微生物群的來源(包括土壤及非人類微生物群)獲得。如本文所提供的，在一些實施例中，自人類微生物群、非人類微生物群、土壤或任何替代來源分離的細菌係在用於本文提供的組成物及方法之前純化。It should be understood that for all compositions provided herein, in some embodiments, the bacterial strain is purified. Thus, for example, the present disclosure provides a purified bacterial strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26. In addition, for example, the present disclosure provides a composition comprising a purified bacterial strain comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26. The bacterial strains disclosed herein may have been originally obtained and purified from the microbiota of one or more human individuals, or from sources other than human microbiota, including soil and non-human microbiota. As provided herein, in some embodiments, bacterial lines isolated from the human microbiome, non-human microbiome, soil, or any alternative source are purified prior to use in the compositions and methods provided herein.

在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，其中該一或多種細菌菌株包含具有選自由SEQ ID NO:1-26組成之群的核酸序列之16S rDNA序列。在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，其中該一或多種細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%同源性之16S rDNA序列。如先前所述，在一些實施例中，細菌菌株經純化。因此，在一個態樣中，本揭示內容提供包含一或多種純化細菌菌株之組成物，其中該一或多種純化細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%同源性之16S rDNA序列。在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，其中該一或多種細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。如先前所述，在一些實施例中，細菌菌株經純化。因此，在一個態樣中，本揭示內容提供包含一或多種純化細菌菌株之組成物，其中該一或多種純化細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。In one aspect, the disclosure provides a composition comprising one or more bacterial strains, wherein the one or more bacterial strains comprise a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26. In one aspect, the disclosure provides a composition comprising one or more bacterial strains, wherein the one or more bacterial strains comprise at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26 16S rDNA sequence. As described previously, in some embodiments, the bacterial strain is purified. Therefore, in one aspect, the present disclosure provides a composition comprising one or more purified bacterial strains, wherein the one or more purified bacterial strains comprise a nucleic acid sequence having at least one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1-26 16S rDNA sequence with 97% homology. In one aspect, the disclosure provides a composition comprising one or more bacterial strains, wherein the one or more bacterial strains comprise a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26 having at least 97% sequence identity 16S rDNA sequence. As described previously, in some embodiments, the bacterial strain is purified. Therefore, in one aspect, the present disclosure provides a composition comprising one or more purified bacterial strains, wherein the one or more purified bacterial strains comprise a nucleic acid sequence having at least one nucleotide sequence selected from the group consisting of SEQ ID NOs: 1-26 16S rDNA sequence with 97% sequence identity.

在一個態樣中，本揭示內容提供包含兩種或更多種純化細菌菌株之組成物，其中該兩種或更多種純化細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%同源性之16S rDNA序列。如上文論述的，在一些實施例中，細菌菌株為組成物之活性成分。因此，在一些實施例中，本揭示內容提供包含作為活性成分的兩種或更多種純化細菌菌株之組成物，其中該兩種或更多種純化細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%同源性之16S rDNA序列。In one aspect, the present disclosure provides a composition comprising two or more purified bacterial strains, wherein the two or more purified bacterial strains comprise a compound selected from the group consisting of SEQ ID NOs: 1-26 The nucleic acid sequence has a 16S rDNA sequence with at least 97% homology. As discussed above, in some embodiments, the bacterial strain is the active ingredient of the composition. Accordingly, in some embodiments, the present disclosure provides a composition comprising two or more purified bacterial strains as active ingredients, wherein the two or more purified bacterial strains comprise a compound selected from the group consisting of SEQ ID NO: 1 The nucleic acid sequence of the group -26 has a 16S rDNA sequence with at least 97% homology.

在一個態樣中，本揭示內容提供包含兩種或更多種純化細菌菌株之組成物，其中該兩種或更多種純化細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。如上文論述的，在一些實施例中，細菌菌株為組成物之活性成分。因此，在一些實施例中，本揭示內容提供包含作為活性成分的兩種或更多種純化細菌菌株之組成物，其中該兩種或更多種純化細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。In one aspect, the present disclosure provides a composition comprising two or more purified bacterial strains, wherein the two or more purified bacterial strains comprise a compound selected from the group consisting of SEQ ID NOs: 1-26 The nucleic acid sequence has a 16S rDNA sequence with at least 97% sequence identity. As discussed above, in some embodiments, the bacterial strain is the active ingredient of the composition. Accordingly, in some embodiments, the present disclosure provides a composition comprising two or more purified bacterial strains as active ingredients, wherein the two or more purified bacterial strains comprise a compound selected from the group consisting of SEQ ID NO: 1 The nucleic acid sequence of the -26 group has a 16S rDNA sequence with at least 97% sequence identity.

在一個態樣中，本揭示內容提供細菌菌株及細菌菌株之組合，該等細菌菌株與包含選自由SEQ ID NO:1-26組成之群的16S rDNA序列之細菌菌株同源或具有高百分比之同源性。如先前所述，在一些實施例中，細菌菌株經純化。本文揭示的具有包含選自由SEQ ID NO:1-26組成之群的核酸序列之16S rDNA序列的細菌菌株與已在各種資料庫(參見，例如，National Center for Biotechnology Information)中描述的細菌菌株之16S rDNA序列具有高百分比之同源性(例如，大於90%)或序列一致性。表1提供當包含SEQ ID NO:1-26之16S rDNA序列與在公共資料庫中可獲得的細菌物種之16S rDNA序列比較時同源最接近的已知物種。In one aspect, the present disclosure provides a combination of bacterial strains and bacterial strains that are homologous to or have a high percentage of a bacterial strain comprising a 16S rDNA sequence selected from the group consisting of SEQ ID NOs: 1-26 Homology. As described previously, in some embodiments, the bacterial strain is purified. Bacterial strains having a 16S rDNA sequence comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26 and bacterial strains that have been described in various databases (see, for example, National Center for Biotechnology Information) are disclosed herein. 16S rDNA sequences have a high percentage of homology (e.g., greater than 90%) or sequence identity. Table 1 provides the known species that are most homologous when comparing the 16S rDNA sequence comprising SEQ ID NOs: 1-26 to the 16S rDNA sequence of a bacterial species available in a public database.

舉例而言，本文揭示的包含具有SEQ ID NO:1之16S rDNA序列之細菌菌株與如NCBI Accession # LN998073 (具有16S rDNA序列SEQ ID NO:27)定義的物種糞考拉桿菌之細菌菌株具有最高同源性。儘管具有SEQ ID NO:1之細菌菌株亦與其他公開的細菌菌株具有同源性，但最高同源性係與如NCBI Accession # LN998073定義的物種糞考拉桿菌之細菌菌株而言。應瞭解，本文揭示的多個細菌菌株可與相同物種具有最高同源性。For example, the bacterial strain disclosed herein comprising a 16S rDNA sequence having SEQ ID NO: 1 and a strain of Koalabacterium faecium as defined by NCBI Accession # LN998073 (having 16S rDNA sequence SEQ ID NO: 27) has the highest Homology. Although the bacterial strain having SEQ ID NO: 1 also has homology with other disclosed bacterial strains, the highest homology is with the bacterial strain of the species Koalabacterium faecium as defined by NCBI Accession # LN998073. It should be understood that multiple bacterial strains disclosed herein may have the highest homology to the same species.

應進一步瞭解，本文揭示的具有包含選自由SEQ ID NO:1-26組成之群的核酸序列之16S rDNA序列之細菌菌株亦基於其完整基因組序列或其完整基因組序列之子集與其他菌株同源。It should be further understood that a bacterial strain disclosed herein having a 16S rDNA sequence comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26 is also homologous to other strains based on its complete genomic sequence or a subset of its complete genomic sequence.

因此，應瞭解，在一個態樣中，本揭示內容亦提供包含細菌物種之組成物及方法，該等細菌物種與具有包含選自由SEQ ID NO:1-26組成之群的核酸序列之16S rDNA序列之細菌菌株具有緊密同源性。Therefore, it should be understood that in one aspect, the present disclosure also provides compositions and methods comprising bacterial species and 16S rDNA having a nucleic acid sequence comprising a group selected from the group consisting of SEQ ID NOs: 1-26 Sequences of bacterial strains have close homology.

在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，其中該一或多種細菌菌株具有選自由以下各項組成之群之物種：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。In one aspect, the present disclosure provides a composition comprising one or more bacterial strains, wherein the one or more bacterial strains have a species selected from the group consisting of: Koala faecalis, Clostridium ulcerans, Dolly Bacillus, Bacteroides uniformis, Rare Micrococcus, Paraprevotella xylaniphila, Parabacillus yojei, Allobacterium, Parabacter gordonii, Eubacillus myxobacteria, Parabacillus dirichi, Bacteroides cellulolyticus, Clara Bacteroides, anaerobic coryneform bacteria, Bacteroides selenoides, Bacteroides fragile, Bacteroides spp., B. escherichia, Clostridium, B. archaebacterium, Bacteroides, Trichomonas bacteria HGA0140 , Hungatella hathewayi, Clostridium lavas, Rumenococcus and Clostridium harmless.

在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，其中該一或多種細菌菌株具有選自由以下各項組成之群之物種：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌；單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。In one aspect, the present disclosure provides a composition comprising one or more bacterial strains, wherein the one or more bacterial strains have a species selected from the group consisting of: Koala faecalis, Clostridium ulcerans, Dolly Bacillus, Bacteroides uniformis, Rare Micrococcus, Paraprevotella xylaniphila, Parabacillus yojei, Allobacterium, Parabacter gordonii, Eubacillus myxobacteria, Parabacillus dirichi, Bacteroides cellulolyticus, Clara Bacteroides, anaerobic coryneform bacteria, Bacteroides selenoides, Bacteroides fragile; Bacteroides spp., B. escherichia, Clostridium, B. archaea and Bacteroides.

在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，其中該一或多種細菌菌株具有選自由以下各項組成之群之物種：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising one or more bacterial strains, wherein the one or more bacterial strains have a species selected from the group consisting of: Koala faecalis, Clostridium ulcerans, Dolly Bacillus, Bacteroides monomorphum, Rare Micrococcus, Paraprevotella xylaniphila, Parabacillus yojei, Allobacterium, Parabacter gordonii, Eumycobacterium myxobacteria, and Paramycobacterium dirichi.

在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，其中該一或多種細菌菌株具有選自由以下各項組成之群之物種：解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。In one aspect, the present disclosure provides a composition comprising one or more bacterial strains, wherein the one or more bacterial strains have a species selected from the group consisting of: B. cellulolyticus, B. cladii, Corynebacterium faecalis, Bacteroides selenoides, Bacteroides fragile, Bacteroides morphogenes, Bacteroides escherichia, Clostridium, Pseudomonas archaea, Bacteroides, Trichomonas bacteria HGA0140, Hungatella hathewayi , Clostridium lavas, Rumenococcus and Clostridium harmless.

在一個態樣中，本揭示內容提供包含一或多種細菌菌株之組成物，其中該一或多種細菌菌株具有選自由以下各項組成之群之物種：解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。In one aspect, the present disclosure provides a composition comprising one or more bacterial strains, wherein the one or more bacterial strains have a species selected from the group consisting of: B. cellulolyticus, B. cladii, Corynebacterium faecalis, Bacteroides selenoides, Bacteroides fragile, Bacteroides morphogenes, Bacteroides escherichia, Clostridium, B. archaebacterium and Bacteroides.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer Bacillus, B. doryi, B. monomorpha, R. micrococcus, Paraprevotella xylaniphila, B. yojei, Isoformis, B. gordonii, Eumycobacterium myxobacteria, B. mycoides, B. dirichi, Cellulolytic Bacillus, B. clarkii, Anaerobic corynebacterium, B. sels, B. fragile, B. haploid, B. escherichia, Clostridium, B. archaea, B. bacterium, Wool spiral Mycobacteria HGA0140, Hungatella hathewayi, Clostridium lavas, Rumenococcus and Clostridium harmless. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23 , At least 24, at least 25, or at least 26 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer Bacillus, B. doryi, B. monomorpha, R. micrococcus, Paraprevotella xylaniphila, B. yojei, Isoformis, B. gordonii, Eumycobacterium myxobacteria, B. mycoides, B. dirichi, Cellulolytic Bacillus, B. clarkii, Anaerobic corynebacterium, B. selenoides, B. fragile, B. haploid, B. escherichia, Clostridium, B. archaea and B. bacterium. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 or at least 21 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer Bacillus, B. doryi, B. monomorpha, R. micrococcus, Paraprevotella xylaniphila, B. yojei, I. bacterium, B. gordonii, E. myxoides and B. dirichi. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising Koala faecalis, Clostridium ulcerans, Bacteroides dorsii, Bacteroides monomorphum, Rare micrococcus, Paraprevotella xylaniphila, about Paracoccus spp., Allobacterium spp., Paracoccus gordonii, Eubacillus mucus and Paracoccus difficile.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of: Koala faecalis, Clostridium ulcerans, Bacteroides doelis, Bacteroides monomorphum, Rare micrococcus , Paraprevotella xylaniphila, B. yojei, Isobacterium, B. gordonii, E. myxobacteria, and B. dirichi.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、考拉桿菌屬CAG:207、潰瘍梭桿菌、可變梭桿菌、多利擬桿菌、福魯克斯擬桿菌、單形擬桿菌、擬桿菌屬D20、罕見小球菌屬、Ruthenibacterium lactatiformans、瘤胃菌科細菌cv2、Gemminger formicilis、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、替莫尼斯別樣桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、副擬桿菌屬HGS0025、黏液真桿菌、副擬桿菌屬CAG:2及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Koala genus CAG : 207, Clostridium ulcerans, Clostridium mutans, Bacteroides doulis, B. fuchsii, B. monomorpha, B. bacterium D20, Rare micrococcus, Ruthenibacterium lactatiformans, Rumenaceae bacteria cv2, Gemminger formicilis, Paraprevotella xylaniphila, Bacteroides yojei, Bacteroides, Bacteroides timmonis, Bacteroides senegal, P. gordonii, Bacteroides HGS0025, Eumycobacterium myxobacteria, CAB: 2 and Paracoccus dieschii. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含： 1) 糞考拉桿菌或考拉桿菌屬CAG:207； 2) 潰瘍梭桿菌或可變梭桿菌； 3) 多利擬桿菌或福魯克斯擬桿菌， 4) 單形擬桿菌或擬桿菌屬D20， 5) 罕見小球菌屬、Ruthenibacterium lactatiformans、瘤胃菌科細菌cv2或Gemminger formicilis， 6) Paraprevotella xylaniphila， 7) 約氏副擬桿菌， 8) 別樣桿菌屬、替莫尼斯別樣桿菌或塞內加爾別樣桿菌， 9) 戈登副擬桿菌或副擬桿菌屬HGS0025， 10) 黏液真桿菌，及 11) 副擬桿菌屬CAG:2或狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising: 1) Koala faecalis or Koala bacterium CAG: 207; 2) Clostridium ulcer or Clostridium mutans; 3) Bacteroides doris or B. fuchsii, 4) Bacteroides or Bacteroides D20, 5) Rare micrococcus, Ruthenibacterium lactatiformans, ruminal bacteria cv2 or Gemminger formicilis, 6) Paraprevotella xylaniphila, 7 ) Pseudomonas yojei, 8) Pseudomonas spp., Pseudomonas timmonis or Pseudomonas senegal, 9) Pseudomonas gordonii or Pseudomonas spp. HGS0025, 10) Eumycobacterium myxoides, and 11) Bacteroides CAG: 2 or Para.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成： 1) 糞考拉桿菌或考拉桿菌屬CAG:207； 2) 潰瘍梭桿菌或可變梭桿菌； 3) 多利擬桿菌或福魯克斯擬桿菌， 4) 單形擬桿菌或擬桿菌屬D20， 5) 罕見小球菌屬、Ruthenibacterium lactatiformans、瘤胃菌科細菌cv2或Gemminger formicilis， 6) Paraprevotella xylaniphila， 7) 約氏副擬桿菌， 8) 別樣桿菌屬、替莫尼斯別樣桿菌或塞內加爾別樣桿菌， 9) 戈登副擬桿菌或副擬桿菌屬HGS0025， 10) 黏液真桿菌，及 11) 副擬桿菌屬CAG:2或狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture consisting of: 1) Koala faecalis or Koala bacterium CAG: 207; 2) Clostridium ulcer or Fusobacterium mutans; 3) Bacteroides doris or B. fuchsii, 4) Bacteroides or Bacteroides D20, 5) Rare micrococcus, Ruthenibacterium lactatiformans, ruminal bacteria cv2 or Gemminger formicilis, 6) Paraprevotella xylaniphila, 7) Pseudomonas yojei, 8) Pseudomonas sp And 11) CAG: 2 or Para.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、可變梭桿菌、多利擬桿菌、單形擬桿菌、Ruthenibacterium lactatiformans、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium mutans, B. doryi, B. haplotype, Ruthenibacterium lactatiformans, Paraprevotella xylaniphila, B. yojei, B. senegalensis, B. gordonii, E. myxoides, and B. dirichi In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含糞考拉桿菌、可變梭桿菌、多利擬桿菌、單形擬桿菌、Ruthenibacterium lactatiformans、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising Koala faecalis, Clostridium mutans, Bifidobacterium dorisi, Bacteroides morphogenes, Ruthenibacterium lactatiformans, Paraprevotella xylaniphila, Yossi Paramycobacterium spp., Senegalese bacterium, Paramycobacterium gordonii, Eumycobacterium myxoidans, and Paramycobacterium dirichli.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成：糞考拉桿菌、可變梭桿菌、多利擬桿菌、單形擬桿菌、Ruthenibacterium lactatiformans、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。In one aspect, the present disclosure provides a composition comprising a mixture of purified bacteria, the purified mixture of bacteria consisting of: Koala faecalis, Clostridium mutans, Bacteroides polymorpha, Bacteroides monomorphum, Ruthenibacterium lactatiformans, Paraprevotella xylaniphila, B. yojei, B. senegalensis, B. gordonii, E. myxobacteria, and B. dirichi.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：考拉桿菌屬CAG:207、潰瘍梭桿菌、多利擬桿菌、擬桿菌屬D20、瘤胃菌科細菌cv2、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、副擬桿菌屬HGS0025、黏液真桿菌及副擬桿菌屬CAG:2。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala bacterium CAG: 207, Fusarium ulcer Bacillus, B. doryi, Bacteroides D20, rumenaceae bacteria cv2, Paraprevotella xylaniphila, Parabacter yojei, B. senegalensis, Bacteroides genus HGS0025, Eumycobacterium myxoids and CAG: 2. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含考拉桿菌屬CAG:207、潰瘍梭桿菌、多利擬桿菌、擬桿菌屬D20、瘤胃菌科細菌cv2、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、副擬桿菌屬HGS0025、黏液真桿菌及副擬桿菌屬CAG:2。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising Koalas CAG: 207, Clostridium ulcerans, Bacteroides dorisi, Bacteroides D20, Rumenaceae bacteria cv2, Paraprevotella xylaniphila, Pseudomonas yojei, Pseudomonas senegales, Pseudomonas HGS0025, Eumycobacterium myxoides and CAG: 2.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物由以下各項組成：考拉桿菌屬CAG:207、潰瘍梭桿菌、多利擬桿菌、擬桿菌屬D20、瘤胃菌科細菌cv2、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、副擬桿菌屬HGS0025、黏液真桿菌及副擬桿菌屬CAG:2。In one aspect, the present disclosure provides a composition comprising a mixture of purified bacteria, the purified mixture of bacteria consisting of: Koala CAG: 207, Clostridium ulcerans, Bacteroides doris, Bacteroides D20, rumen The mycobacterial bacteria cv2, Paraprevotella xylaniphila, Parabacter yojei, Albinobacterium senegal, Homogeneus HGS0025, Eumycobacterium myxoidum and CAG: 2.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、考拉桿菌屬CAG:207、潰瘍梭桿菌、可變梭桿菌、多利擬桿菌、福魯克斯擬桿菌、單形擬桿菌、擬桿菌屬D20、罕見小球菌屬、Ruthenibacterium lactatiformans、瘤胃菌科細菌cv2、Gemminger formicilis、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、替莫尼斯別樣桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、副擬桿菌屬HGS0025、黏液真桿菌、副擬桿菌屬CAG:2及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, koala Bacillus CAG: 207, Clostridium ulcerans, Clostridium mutans, Bacteroides doelis, B. fuchsii, B. monomorpha, Bacteroides D20, Rare micrococcus, Ruthenibacterium lactatiformans, Rumenaceae bacteria cv2, Gemminger formicilis, Paraprevotella xylaniphila, Parabivois yojei, Isobacterium, Timonis : 2 and B. dickii. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、可變梭桿菌、多利擬桿菌、單形擬桿菌、Ruthenibacterium lactatiformans、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, variable Clostridium, B. doryi, B. monomorpha, Ruthenibacterium lactatiformans, Paraprevotella xylaniphila, B. yojei, P. senegalensis, P. gordonii, Pseudomonas myxobacteria, and P. dirichi In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：考拉桿菌屬CAG:207、潰瘍梭桿菌、多利擬桿菌、擬桿菌屬D20、瘤胃菌科細菌cv2、Paraprevotella xylaniphila、約氏副擬桿菌、塞內加爾別樣桿菌、副擬桿菌屬HGS0025、黏液真桿菌及副擬桿菌屬CAG:2。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala bacterium CAG: 207 , Clostridium ulcerans, Bacterium dorisi, Bacteroides D20, rumenaceae bacteria cv2, Paraprevotella xylaniphila, Parabacter yojei, Alternaria senegal, Paramycobacteria HGS0025, Eumycobacterium myxoides and CAG paramycobacterium 2. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 or at least 11 strains of bacteria.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Bacterobacterium cellulolyticus, Carat Bacteroides spp., Anaerobic faecalis, Bacteroides selenoides, B. fragile, B. haplotypes, B. escherichia, Clostridium, B. archaea, Bacteroides, Trichomonas bacteria HGA0140, Hungatella hathewayi, Clostridium lavas, Rumenococcus and Clostridium harmless. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least Eleven, at least 12, at least 13, at least 14, or at least 15 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Bacterobacterium cellulolyticus, Carat Bacteroides spp., Anaerobic Corynebacterium faecalis, B. selenoides, B. fragile, B. haplotypes, B. escherichia, Clostridium, B. archaea and B. bacterium In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten bacterial strains .

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、罕見小球菌屬及黏液真桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種或至少4種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer Bacillus, Rare Micrococcus and Eumycobacterium myxoidum. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least 3 or at least 4 bacterial strains.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之兩種或更多種細菌菌株：多利擬桿菌、單形擬桿菌、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌及狄氏副擬桿菌。在本文提供的組成物之一些實施例中，該純化細菌混合物包含至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising two or more bacterial strains selected from the group consisting of: Bacteroides doelis, P. monomorpha Bacillus spp., Paraprevotella xylaniphila, B. yoichii, Isobacterium spp., B. gordonii, and B. dickensii. In some embodiments of the compositions provided herein, the purified bacterial mixture comprises at least three, at least four, at least five, at least six, or at least seven bacterial strains.

應瞭解，組成物可包括特定物種之多個菌株。因此，為說明，本文揭示的組成物之非限制性實例包含塞爾氏擬桿菌之一個菌株及單形擬桿菌之兩個菌株。It should be understood that the composition may include multiple strains of a particular species. Thus, for illustration, non-limiting examples of the compositions disclosed herein include one strain of B. selsei and two strains of B. morphogenes.

本揭示內容亦涵蓋包含與以下物種同源性緊密及/或屬於以下物種的細菌菌株之組成物：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。This disclosure also encompasses compositions that include bacterial strains that are closely homologous to and / or belong to the following species: Koala faecalis, Clostridium ulcerans, Bacteroides polymorpha, Bacteroides monomorphum, Rare micrococcus, Paraprevotella xylaniphila, Pseudomonas yojei, Pseudomonas sp Bacteroides, Bacteroides fragile, Bacteroides escherichia, Clostridium, Parabacillus archaea, Bacteroides, Trichomonas bacteria HGA0140, Hungatella hathewayi, Clostridium lavas, Rumenococcus and Harmless Clostridium.

因此，在一個實施例中，本揭示內容之組成物包括一或多種細菌菌株，該等細菌菌株包含與選自由SEQ ID NO:27-52組成之群的核酸序列具有至少97%同源性之16S rDNA序列。在一些實施例中，本揭示內容之組成物包括兩種或更多種細菌菌株，該等細菌菌株包含與選自由SEQ ID NO:27-52組成之群的核酸序列具有至少97%同源性之16S rDNA序列。Therefore, in one embodiment, the composition of the present disclosure includes one or more bacterial strains comprising a bacterial strain having at least 97% homology with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 27-52. 16S rDNA sequence. In some embodiments, the composition of the present disclosure includes two or more bacterial strains comprising at least 97% homology with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 27-52 16S rDNA sequence.

因此，在一個實施例中，本揭示內容之組成物包括一或多種細菌菌株，該等細菌菌株包含與選自由SEQ ID NO:27-52組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。在一些實施例中，本揭示內容之組成物包括兩種或更多種細菌菌株，該等細菌菌株包含與選自由SEQ ID NO:27-52組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。Therefore, in one embodiment, the composition of the present disclosure includes one or more bacterial strains comprising a nucleic acid sequence having at least 97% sequence identity with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 27-52. 16S rDNA sequence. In some embodiments, the composition of the present disclosure includes two or more bacterial strains comprising at least 97% sequence identity with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 27-52 16S rDNA sequence.

在一個態樣中，本揭示內容之組成物包括兩種或更多種純化細菌菌株，該等純化細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%同源性之16S rDNA序列。在一些實施例中，本揭示內容之組成物包括兩種或更多種純化細菌菌株，該等純化細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。在一些實施例中，本揭示內容之組成物包括選自由以下各項組成之群的物種之兩種或更多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。在一些實施例中，本揭示內容之組成物包括兩種或更多種純化細菌菌株，該等細菌菌株包含與選自由SEQ ID NO:27-52組成之群的核酸序列具有至少97%同源性之16S rDNA序列。在一些實施例中，本揭示內容之組成物包括兩種或更多種純化細菌菌株，該等細菌菌株包含與選自由SEQ ID NO:27-52組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。In one aspect, the composition of the present disclosure includes two or more purified bacterial strains comprising at least 97% identity to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26 16S rDNA sequence of origin. In some embodiments, the composition of the present disclosure includes two or more purified bacterial strains comprising at least 97% sequence with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26 Consistent 16S rDNA sequence. In some embodiments, the composition of the present disclosure includes two or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcerans, Bacteroides doelis, Bacteroides monomorphis , Rare Micrococcus, Paraprevotella xylaniphila, Paramycobacterium yojei, Albibacterium, Paramycobacterium gordonii, Eumycobacterium myxoides, Paramycobacterium dirichli, Bacillus cellulolyticus, Bacillus clausii, Anaerobic faeces Coryneform bacteria, Bacteroides fragrans, Bacteroides fragile, Bacteroides morphogenes, Bacteroides escherichia, Clostridium, Pseudomonas archaea, Bacteroides, Trichomonas bacteria HGA0140, Hungatella hathewayi, Lava Clostridium, Rumenococcus and harmless Clostridium. In some embodiments, the composition of the present disclosure includes two or more purified bacterial strains comprising at least 97% homology to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 27-52 16S rDNA sequence. In some embodiments, the composition of the present disclosure includes two or more purified bacterial strains comprising at least 97% sequence identity with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 27-52 16S rDNA sequence.

在一些實施例中，本揭示內容提供具有兩種或更多種純化細菌菌株之組成物，該等細菌菌株包含具有選自由SEQ ID NO:1-26組成之群的核酸序列之16S rDNA序列。在一些實施例中，本揭示內容提供具有五種或更多種純化細菌菌株之組成物，該等細菌菌株包含具有選自由SEQ ID NO:1-26組成之群的核酸序列之16S rDNA序列。在一些實施例中，本揭示內容提供具有至少十種純化細菌菌株之組成物，其中該等細菌菌株包含分別具有核酸序列SEQ ID NO:1-26之16S rDNA序列。在一些實施例中，本揭示內容提供由十種純化細菌菌株組成之組成物，其中該等細菌菌株包含分別具有核酸序列SEQ ID NO:1-26之16S rDNA序列。在一些實施例中，本揭示內容提供基本上由十一種純化細菌菌株組成之組成物，其中該等細菌菌株包含分別具有核酸序列SEQ ID NO:1-26之16S rDNA序列。如本文所使用，基本上由...組成係指組成物不包括另外的細菌菌株。In some embodiments, the present disclosure provides a composition having two or more purified bacterial strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26. In some embodiments, the present disclosure provides a composition having five or more purified bacterial strains comprising a 16S rDNA sequence having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26. In some embodiments, the present disclosure provides a composition having at least ten purified bacterial strains, wherein the bacterial strains comprise 16S rDNA sequences each having a nucleic acid sequence of SEQ ID NOs: 1-26. In some embodiments, the present disclosure provides a composition consisting of ten purified bacterial strains, wherein the bacterial strains comprise 16S rDNA sequences each having a nucleic acid sequence of SEQ ID NOs: 1-26. In some embodiments, the present disclosure provides a composition consisting essentially of eleven purified bacterial strains, wherein the bacterial strains comprise 16S rDNA sequences each having a nucleic acid sequence of SEQ ID NOs: 1-26. As used herein, consisting essentially of means that the composition does not include additional bacterial strains.

在一些實施例中，本揭示內容提供具有細菌菌株之組成物，該等細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%同源性之16S rDNA序列。在一些實施例中，本揭示內容提供具有兩種或更多種純化細菌菌株之組成物，該等細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%同源性之16S rDNA序列。在一些實施例中，本揭示內容提供具有五種或更多種純化細菌菌株之組成物，該等細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%同源性之16S rDNA序列。在一些實施例中，本揭示內容提供具有至少十種純化細菌菌株之組成物，其中該等細菌菌株包含分別與核酸序列SEQ ID NO:1-26具有至少97%同源性之16S rDNA序列。在一些實施例中，本揭示內容提供由十種純化細菌菌株組成之組成物，其中該等細菌菌株包含分別與核酸序列SEQ ID NO:1-26具有至少97%同源性之16S rDNA序列。在一些實施例中，本揭示內容提供基本上由十種純化細菌菌株組成之組成物，其中該等細菌菌株包含分別與核酸序列SEQ ID NO:1-26具有至少97%同源性之16S rDNA序列。In some embodiments, the present disclosure provides a composition having a bacterial strain comprising a 16S rDNA sequence having at least 97% homology with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26. In some embodiments, the present disclosure provides a composition having two or more purified bacterial strains comprising at least 97% identity to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26 16S rDNA sequence of origin. In some embodiments, the present disclosure provides a composition having five or more purified bacterial strains comprising at least 97% identity with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26 16S rDNA sequence of origin. In some embodiments, the present disclosure provides a composition having at least ten purified bacterial strains, wherein the bacterial strains each comprise a 16S rDNA sequence having at least 97% homology with the nucleic acid sequence SEQ ID NOs: 1-26. In some embodiments, the present disclosure provides a composition consisting of ten purified bacterial strains, wherein the bacterial strains each comprise a 16S rDNA sequence having at least 97% homology with the nucleic acid sequence SEQ ID NOs: 1-26. In some embodiments, the present disclosure provides a composition consisting essentially of ten purified bacterial strains, wherein the bacterial strains comprise 16S rDNA with at least 97% homology to the nucleic acid sequence SEQ ID NO: 1-26, respectively. sequence.

在一些實施例中，本揭示內容提供具有細菌菌株之組成物，該等細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。在一些實施例中，本揭示內容提供具有兩種或更多種純化細菌菌株之組成物，該等細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。在一些實施例中，本揭示內容提供具有五種或更多種純化細菌菌株之組成物，該等細菌菌株包含與選自由SEQ ID NO:1-26組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。在一些實施例中，本揭示內容提供具有至少十種純化細菌菌株之組成物，其中該等細菌菌株包含分別與核酸序列SEQ ID NO:1-26具有至少97%序列一致性之16S rDNA序列。在一些實施例中，本揭示內容提供由十種純化細菌菌株組成之組成物，其中該等細菌菌株包含分別與核酸序列SEQ ID NO:1-26具有至少97%序列一致性之16S rDNA序列。在一些實施例中，本揭示內容提供基本上由十種純化細菌菌株組成之組成物，其中該等細菌菌株包含分別與核酸序列SEQ ID NO:1-26具有至少97%序列一致性之16S rDNA序列。In some embodiments, the present disclosure provides a composition having a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26. In some embodiments, the present disclosure provides a composition having two or more purified bacterial strains comprising a nucleic acid sequence having at least 97% sequence with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26 Consistent 16S rDNA sequence. In some embodiments, the present disclosure provides a composition having five or more purified bacterial strains comprising at least 97% sequence with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-26 Consistent 16S rDNA sequence. In some embodiments, the present disclosure provides a composition having at least ten purified bacterial strains, wherein the bacterial strains each comprise a 16S rDNA sequence having at least 97% sequence identity with the nucleic acid sequence SEQ ID NO: 1-26. In some embodiments, the present disclosure provides a composition consisting of ten purified bacterial strains, wherein the bacterial strains each comprise a 16S rDNA sequence having at least 97% sequence identity with the nucleic acid sequence SEQ ID NOs: 1-26. In some embodiments, the present disclosure provides a composition consisting essentially of ten purified bacterial strains, wherein the bacterial strains comprise 16S rDNA, each having at least 97% sequence identity with the nucleic acid sequence SEQ ID NO: 1-26. sequence.

在一個態樣中，本揭示內容提供包含與以下細菌物種有關的細菌菌株之組成物：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌(參見，例如，表1)。應瞭解，本文揭示的組成物之多個細菌菌株可具有相同的相關細菌物種。在一些實施例中，本揭示內容提供具有兩種或更多種純化細菌菌株之組成物，該等純化細菌菌株包含與選自由SEQ ID NO:27-52組成之群的核酸序列具有至少97%同源性之16S rDNA序列。在一些實施例中，本揭示內容提供具有兩種或更多種純化細菌菌株之組成物，該等純化細菌菌株包含與選自由SEQ ID NO:27-52組成之群的核酸序列具有至少97%序列一致性之16S rDNA序列。In one aspect, the present disclosure provides a composition comprising a bacterial strain related to the following bacterial species: Koala faecalis, Clostridium ulcerans, Bacteroides doelis, B. haplotypes, Rare micrococcus, Paraprevotella xylaniphila, about Pseudomonas spp., Pseudomonas spp., Pseudomonas mycobacterium, Pseudomonas myxobacteria, Pseudomonas diescherii, B. cellulolyticus, B. clarkii, Anaerobic coryneform bacterium, Bacteroides selves, Bacteroides fragile, Bacteroides monocytogenes, Bacteroides escherichia, Clostridium, B. archaea, Bacteroides, Trichomonas bacteria HGA0140, Hungatella hathewayi, Clostridium lavas, Clostridium rumenum, and Clostridium sp. Bacteria (see, for example, Table 1). It should be understood that multiple bacterial strains of the composition disclosed herein may have the same related bacterial species. In some embodiments, the present disclosure provides a composition having two or more purified bacterial strains comprising at least 97% of a nucleic acid sequence with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 27-52 16S rDNA sequence of homology. In some embodiments, the present disclosure provides a composition having two or more purified bacterial strains comprising at least 97% of a nucleic acid sequence with a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 27-52 16S rDNA sequence of sequence identity.

在一個態樣中，本揭示內容提供具有16S rDNA序列之細菌菌株，該等16S rDNA序列與本文描述的細菌菌株或物種之序列中之任一者的核酸序列具有同源性。在一些實施例中，細菌菌株在指定區域上或在整個序列上相對於本文描述的菌株或細菌物種中之任何者具有至少60%、至少70%、至少80%、至少81%、至少82%、至少83%、至少84%、至少85%、至少86%、至少87%、至少88%、至少89%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%、至少99%、至少99.5%、至少99.6%、至少99.7%、至少99.8%、至少99.9%或至多100%同源性。熟習此項技術者應瞭解，在兩種或更多種核酸序列或胺基酸序列之上下文中的術語「同源性」或「同源性百分比」係指兩個或更多個序列或其部分之間的相似性量度。同源性可在序列的長度為至少約50個核苷酸之區域上存在，或更佳地在長度為100至500個或1000個或更多個核苷酸的區域上存在。在一些實施例中，同源性在16S rRNA或16S rDNA序列或其部分之長度上存在。In one aspect, the present disclosure provides a bacterial strain having a 16S rDNA sequence that is homologous to a nucleic acid sequence of any of the sequences of a bacterial strain or species described herein. In some embodiments, the bacterial strain has at least 60%, at least 70%, at least 80%, at least 81%, at least 82% relative to any of the strains or bacterial species described herein over a designated area or over the entire sequence. , At least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or at most 100% homology. Those skilled in the art will understand that the term "homology" or "percent homology" in the context of two or more nucleic acid sequences or amino acid sequences refers to two or more sequences or Similarity measure between parts. Homology may exist over a region of the sequence that is at least about 50 nucleotides in length, or more preferably over a region that is 100 to 500 or 1000 or more nucleotides in length. In some embodiments, homology exists over the length of a 16S rRNA or 16S rDNA sequence or portion thereof.

另外或替代地，可針對兩個或更多個序列之間的一致性評定該等序列。在兩個或更多個核酸或胺基酸序列之上下文中的術語「一致」或「一致性」百分比涉及相同的兩個或更多個序列或子序列。若當針對比較窗口或指定區域上之最大對應性來比較及比對時，如使用以下序列比較演算法之一或藉由手動比對及目測檢查來量測時，兩個序列在指定區域上或在整個序列上具有指定百分比的為相同(例如，至少80%、85%、90%、95%、96%、97%、98%、99%、99.5%、99.6%、99.7%、99.8%或99.9%一致)之胺基酸殘基或核苷酸，則兩個序列為「實質上一致」。視情況，一致性在序列的長度為至少約50個核苷酸之區域上存在，或更佳地在長度為100至500個或1000個或更多個核苷酸的區域上存在。在一些實施例中，一致性在16S rRNA或16S rDNA序列之長度上存在。Additionally or alternatively, the sequences may be assessed for consistency between two or more sequences. The term "consistent" or "percent identity" in the context of two or more nucleic acid or amino acid sequences refers to two or more sequences or subsequences that are the same. When comparing and aligning for the maximum correspondence on the comparison window or specified area, such as using one of the following sequence comparison algorithms or measuring by manual comparison and visual inspection, the two sequences are on the specified area Or having the same percentage across the entire sequence (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8% Or 99.9% identical) amino acid residues or nucleotides, the two sequences are "substantially identical." Optionally, identity exists over a region of the sequence that is at least about 50 nucleotides in length, or more preferably over a region that is 100 to 500 or 1000 or more nucleotides in length. In some embodiments, identity exists over the length of a 16S rRNA or 16S rDNA sequence.

另外或替代地，可針對兩個或更多個序列之間的對準來評定該等序列。在兩個或更多個核酸或胺基酸序列之上下文中的術語「對準」或「對準」百分比涉及相同的兩個或更多個序列或子序列。若當針對比較窗口或指定區域上之最大對應性來比較及比對時，如使用以下序列比較演算法之一或藉由手動比對及目測檢查來量測時，兩個序列在指定區域上或在整個序列上具有指定百分比的為相同(例如，至少80%、85%、90%、95%、96%、97%、98%、99%、99.5%、99.6%、99.7%、99.8%或99.9%一致)之胺基酸殘基或核苷酸，則兩個序列為「實質上對準」。視情況，對準在序列的長度為至少約50個核苷酸之區域上存在，或更佳地在長度為100至500個或1000個或更多個核苷酸的區域上存在。在一些實施例中，一致性在16S rRNA或16S rDNA序列之長度上存在。Additionally or alternatively, the sequences may be assessed for alignment between two or more sequences. The term "aligned" or "percent" in the context of two or more nucleic acid or amino acid sequences refers to two or more sequences or subsequences that are the same. When comparing and aligning for the maximum correspondence on the comparison window or specified area, such as using one of the following sequence comparison algorithms or measuring by manual comparison and visual inspection, the two sequences are on the specified area Or having the same percentage across the entire sequence (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8% Or 99.9% identical) amino acid residues or nucleotides, the two sequences are "substantially aligned." Optionally, the alignment is present over a region of the sequence that is at least about 50 nucleotides in length, or more preferably over a region that is 100 to 500 or 1000 or more nucleotides in length. In some embodiments, identity exists over the length of a 16S rRNA or 16S rDNA sequence.

對於序列比較，典型地一個序列充當一參考序列，將測試序列與之比較。用於比較的序列比對方法在此項技術中為熟知的。參見，例如，Smith及Waterman (1970) Adv. Appl. Math. 2:482c之局部同源性演算法、Needleman及Wunsch，J. Mol. Biol. 48:443，1970之同源性比對演算法、Pearson及Lipman. Proc. Natl. Acad. Sci. USA 85:2444，1988之相似性搜尋方法、該些演算法之電腦化實施方式(Wisconsin Genetics套裝軟體，Genetics Computer Group. Madison. WI中之GAP、BESTFIT、FASTA及TFASTA)或手動比對及目測檢查(參見，例如，Brent等人，Current Protocols in Molecular Biology，John Wiley & Sons，Inc. (Ringbou編，2003))。適用於判定序列一致性百分比及序列相似性的演算法之兩個實例為BLAST及BLAST 2.0演算法，其分別描述於Altschul等人，Nuc. Acids Res. 25:3389-3402，1977；及Altschul等人，J. Mol. Biol. 215:403-410，1990中。For sequence comparison, a sequence typically serves as a reference sequence against which the test sequence is compared. Sequence alignment methods for comparison are well known in the art. See, eg, the local homology algorithm of Smith and Waterman (1970) Adv. Appl. Math. 2: 482c, the homology comparison algorithm of Needleman and Wunsch, J. Mol. Biol. 48: 443, 1970 , Pearson and Lipman. Proc. Natl. Acad. Sci. USA 85: 2444, 1988, similarity search method, computerized implementation of these algorithms (Wisconsin Genetics software package, GAP in Genetics Computer Group. Madison. WI , BESTFIT, FASTA, and TFASTA) or manual alignment and visual inspection (see, eg, Brent et al., Current Protocols in Molecular Biology, John Wiley & Sons, Inc. (ed. Ringbou, 2003)). Two examples of algorithms suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., Nuc. Acids Res. 25: 3389-3402, 1977; and Altschul et al. Human, J. Mol. Biol. 215: 403-410, 1990.

在一個態樣中，本揭示內容提供包含多種純化細菌菌株之組成物。在一個態樣中，將組成物之純化細菌菌株之16S rDNA序列與細菌基因組資料庫中之已知細菌物種/菌株中16S rDNA序列相比以識別與本文揭示的細菌菌株最接近的已知相關細菌物種(參見，例如，表1及表2A)。應瞭解，本文揭示的組成物之多個細菌菌株可具有相同的最接近相關細菌物種。在一個態樣中，本揭示內容提供包含具有16S rDNA序列之一或多種細菌菌株或物種之組成物，該等16S rDNA序列與藉由SEQ ID NO:1-26提供的序列中之任一者之核酸序列具有同源性。在一些實施例中，具有與本文描述的菌株中任何者之最接近相關物種中任一者的核酸序列具有同源性之16S rDNA序列之物種相應於具有藉由SEQ ID NO:27-52提供的16S rDNA序列之細菌菌株。在一個態樣中，本揭示內容提供包含具有16S rDNA序列之一或多種細菌菌株或物種之組成物，該等16S rDNA序列與藉由SEQ ID NO:1-21提供的序列中之任一者之核酸序列具有同源性。在一些實施例中，具有與本文描述的菌株中任何者之最接近相關物種中任一者的核酸序列具有同源性之16S rDNA序列之物種相應於具有藉由SEQ ID NO:27-47提供的16S rDNA序列之細菌菌株。在一個態樣中，本揭示內容提供包含具有16S rDNA序列之一或多種細菌菌株或物種之組成物，該等16S rDNA序列與藉由SEQ ID NO:1-11提供的序列中之任一者之核酸序列具有同源性。在一些實施例中，具有與本文描述的菌株中任何者之最接近相關物種中任一者的核酸序列具有同源性之16S rDNA序列之物種相應於具有藉由SEQ ID NO:27-37提供的16S rDNA序列之細菌菌株。在一個態樣中，本揭示內容提供包含具有16S rDNA序列之一或多種細菌菌株或物種之組成物，該等16S rDNA序列與藉由SEQ ID NO:12-26提供的序列中之任一者之核酸序列具有同源性。在一些實施例中，具有與本文描述的菌株中任何者之最接近相關物種中任一者的核酸序列具有同源性之16S rDNA序列之物種相應於具有藉由SEQ ID NO:38-52提供的16S rDNA序列之細菌菌株。在一個態樣中，本揭示內容提供包含具有16S rDNA序列之一或多種細菌菌株或物種之組成物，該等16S rDNA序列與藉由SEQ ID NO:12-21提供的序列中之任一者之核酸序列具有同源性。在一些實施例中，具有與本文描述的菌株中任何者之最接近相關物種中任一者的核酸序列具有同源性之16S rDNA序列之物種相應於具有藉由SEQ ID NO:38-47提供的16S rDNA序列之細菌菌株。In one aspect, the disclosure provides a composition comprising a plurality of purified bacterial strains. In one aspect, the 16S rDNA sequence of the purified bacterial strain of the composition is compared to the 16S rDNA sequence in a known bacterial species / strain in the bacterial genome database to identify the closest known correlation with the bacterial strain disclosed herein Bacterial species (see, for example, Table 1 and Table 2A). It should be understood that multiple bacterial strains of the composition disclosed herein may have the same closest relevant bacterial species. In one aspect, the present disclosure provides a composition comprising one or more bacterial strains or species having a 16S rDNA sequence, any of the 16S rDNA sequence and the sequence provided by SEQ ID NOs: 1-26 The nucleic acid sequences have homology. In some embodiments, a species having a 16S rDNA sequence that has homology to the nucleic acid sequence of any of the strains described herein that are closest to any of the related species corresponds to having a sequence provided by SEQ ID NOs: 27-52 16S rDNA sequence of a bacterial strain. In one aspect, the present disclosure provides a composition comprising one or more bacterial strains or species having a 16S rDNA sequence, any of the 16S rDNA sequence and the sequence provided by SEQ ID NOs: 1-21 The nucleic acid sequences have homology. In some embodiments, a species having a 16S rDNA sequence that has homology to the nucleic acid sequence of any of the strains described herein that is closest to any of the related species corresponds to having a sequence provided by SEQ ID NOs: 27-47 16S rDNA sequence of a bacterial strain. In one aspect, the present disclosure provides a composition comprising one or more bacterial strains or species having a 16S rDNA sequence, any of the 16S rDNA sequence and the sequence provided by SEQ ID NOs: 1-11 The nucleic acid sequences have homology. In some embodiments, a species having a 16S rDNA sequence that has homology to the nucleic acid sequence of any of the strains described herein that are closest to any of the related species corresponds to having a sequence provided by SEQ ID NOs: 27-37 16S rDNA sequence of a bacterial strain. In one aspect, the present disclosure provides a composition comprising one or more bacterial strains or species having a 16S rDNA sequence, any of the 16S rDNA sequence and the sequence provided by SEQ ID NOs: 12-26 The nucleic acid sequences have homology. In some embodiments, a species having a 16S rDNA sequence with homology to the nucleic acid sequence of any of the strains described herein that is closest to any of the related species corresponds to having a sequence provided by SEQ ID NOs: 38-52 16S rDNA sequence of a bacterial strain. In one aspect, the present disclosure provides a composition comprising one or more bacterial strains or species having a 16S rDNA sequence, any of the 16S rDNA sequence and the sequence provided by SEQ ID NOs: 12-21 The nucleic acid sequences have homology. In some embodiments, a species having a 16S rDNA sequence that has homology to the nucleic acid sequence of any of the strains described herein that are closest to any of the related species corresponds to having a sequence provided by SEQ ID NOs: 38-47 16S rDNA sequence of a bacterial strain.

在一些實施例中，本文揭示的組成物提供本文描述的細菌菌株(例如，純化細菌菌株)中之至少一者。在一些實施例中，包含至少一種細菌菌株之組成物包含具有選自SEQ ID NO:1-26中之任一者的16S rDNA序列之至少一種細菌菌株。在一些實施例中，包含至少一種細菌菌株之組成物包含與選自SEQ ID NO:1-26中之任一者的16S rDNA序列具有97%同源性之至少一種細菌菌株。在一些實施例中，包含至少一種細菌菌株之組成物包含與選自SEQ ID NO:1-26中之任一者的16S rDNA序列具有97%序列一致性之至少一種細菌菌株。In some embodiments, the compositions disclosed herein provide at least one of the bacterial strains (eg, purified bacterial strains) described herein. In some embodiments, the composition comprising at least one bacterial strain comprises at least one bacterial strain having a 16S rDNA sequence selected from any one of SEQ ID NOs: 1-26. In some embodiments, the composition comprising at least one bacterial strain comprises at least one bacterial strain having 97% homology to a 16S rDNA sequence selected from any one of SEQ ID NOs: 1-26. In some embodiments, the composition comprising at least one bacterial strain comprises at least one bacterial strain having 97% sequence identity to a 16S rDNA sequence selected from any one of SEQ ID NOs: 1-26.

在一些實施例中，本文揭示的組成物包含兩種或更多種細菌菌株。在一些實施例中，本文描述的組成物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種或至少20種或更多種細菌菌株(例如，純化細菌菌株)。In some embodiments, a composition disclosed herein comprises two or more bacterial strains. In some embodiments, the compositions described herein comprise at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven Species, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 or more bacterial strains (e.g., purified bacterial strains) .

在本文提供的組成物之一些實施例中，至少50%之細菌菌株屬於擬桿菌目。在本文提供的組成物之一些實施例中，至少50%之細菌菌株屬於擬桿菌屬或副擬桿菌屬。在本文提供的組成物之一些實施例中，一或多種菌株屬於擬桿菌屬且一或多種菌株屬於副擬桿菌屬。在本文提供的組成物之一些實施例中，細菌菌株之至少25%屬於擬桿菌科。在本文提供的組成物之一些實施例中，細菌菌株中之一或多者屬於擬桿菌屬。在本文提供的組成物之一些實施例中，細菌菌株中之一或多者屬於副擬桿菌屬。In some embodiments of the compositions provided herein, at least 50% of the bacterial strains belong to the order Bacteroides. In some embodiments of the compositions provided herein, at least 50% of the bacterial strains belong to the genus Bacteroides or Parabacteria. In some embodiments of the compositions provided herein, one or more strains belong to the genus Bacteroides and one or more strains belong to the genus Parabacterus. In some embodiments of the compositions provided herein, at least 25% of the bacterial strains belong to the family Bacteroides. In some embodiments of the compositions provided herein, one or more of the bacterial strains belong to the genus Bacteroides. In some embodiments of the compositions provided herein, one or more of the bacterial strains belong to the genus Parabacterium.

在本文提供的組成物之一些實施例中，該組成物不包括屬於擬桿菌目之細菌菌株。In some embodiments of the composition provided herein, the composition does not include a bacterial strain belonging to the order Bacteroides.

在本文提供的組成物之一些實施例中，細菌菌株中之一或多者屬於擬桿菌目，且細菌菌株中之一或多者屬於梭菌目。在本文提供的組成物之一些實施例中，至少50%之細菌菌株屬於擬桿菌目，且細菌菌株中之一或多者屬於梭菌目。在本文提供的組成物之一些實施例中，至少75%之細菌菌株屬於擬桿菌目，且細菌菌株中之一或多者屬於梭菌目。在本文提供的組成物之一些實施例中，至少90%之細菌菌株屬於擬桿菌目，且細菌菌株中之一或多者屬於梭菌目。In some embodiments of the compositions provided herein, one or more of the bacterial strains belong to the order Bacteroides, and one or more of the bacterial strains belong to the order Clostridia. In some embodiments of the compositions provided herein, at least 50% of the bacterial strains belong to the order Bacteroides, and one or more of the bacterial strains belong to the order Clostridia. In some embodiments of the compositions provided herein, at least 75% of the bacterial strains belong to the order Bacteroides, and one or more of the bacterial strains belong to the order Clostridia. In some embodiments of the compositions provided herein, at least 90% of the bacterial strains belong to the order Bacteroides, and one or more of the bacterial strains belong to the order Clostridia.

在一些實施例中，本文提供的組成物不包括大腸桿菌。在一些實施例中，本文提供的組成物不包括雙叉桿菌。在一些實施例中，本文提供的組成物不包括桿菌。在一些實施例中，本文提供的組成物不包括腸球菌。在一些實施例中，本文提供的組成物不包括Barnesiella 。在一些實施例中，本文提供的組成物不包括脆弱擬桿菌。在一些實施例中，本文提供的組成物不包括多形擬桿菌。在一些實施例中，本文提供的組成物不包括阿克曼氏菌。在一些實施例中，本文提供的組成物不包括變形菌門(Proteobacteria)。在一些實施例中，本文提供的組成物不包括伯克氏菌。在一些實施例中，本文提供的組成物不包括屬於集IV之梭菌種。在一些實施例中，本文提供的組成物不包括糞便菌(Faecalibacterium )。在一些實施例中，本文提供的組成物不包括屬於集群XIVa之梭菌種。在一些實施例中，組成物不包含真菌，諸如莫奈裡菌種(Monilla species)。In some embodiments, the compositions provided herein do not include E. coli. In some embodiments, the compositions provided herein do not include Bifidobacterium. In some embodiments, the compositions provided herein do not include Bacillus. In some embodiments, the compositions provided herein do not include enterococci. In some embodiments, the compositions provided herein do not include Barnesiella . In some embodiments, the compositions provided herein do not include B. fragile. In some embodiments, the compositions provided herein do not include B. polymorpha. In some embodiments, the compositions provided herein do not include Ackermania. In some embodiments, the compositions provided herein do not include Proteobacteria. In some embodiments, the compositions provided herein do not include Burkholderia. In some embodiments, the compositions provided herein do not include Clostridium species belonging to Set IV. In some embodiments, the compositions provided herein do not include Faecalibacterium . In some embodiments, the compositions provided herein do not include Clostridium species belonging to cluster XIVa. In some embodiments, the composition does not include a fungus, such as a Monilla species.

在一個態樣中，本揭示內容提供人類糞便樣本中可誘導CD8 T細胞的純化餾分。In one aspect, the present disclosure provides purified fractions of human feces samples that can induce CD8 T cells.

在本文提供的組成物之一些實施例中，細菌菌株中之一或多者為人類來源之細菌。在本文提供的組成物之一些實施例中，所有細菌菌株為人類來源之細菌。在本文提供的組成物之一些實施例中，細菌菌株係來源於多於一種人類供體。In some embodiments of the compositions provided herein, one or more of the bacterial strains are bacteria of human origin. In some embodiments of the compositions provided herein, all bacterial strains are bacteria of human origin. In some embodiments of the compositions provided herein, the bacterial strain is derived from more than one human donor.

用於本文提供的組成物中之細菌菌株通常係自健康個體之微生物群分離。在一些實施例中，組成物包括來源於單一個體之菌株。在一些實施例中，組成物包括來源於多個個體之菌株。在一些實施例中，細菌菌株係自多個個體獲得，分離且單獨地生長。單獨生長的細菌組成物可隨後組合來提供本揭示內容之組成物。應瞭解，本文提供的組成物之細菌菌株之起源不限於來自健康個體之人類微生物群。在一些實施例中，細菌菌株來源於具有呈腸道菌叢擾亂之微生物群的人類。在一些實施例中，細菌菌株來源於非人類動物或環境(例如，土壤或地表水)。在一些實施例中，本文提供的細菌菌株之組合來源於多個來源(例如，人類及非人類動物)。Bacterial strains used in the compositions provided herein are typically isolated from the microbiota of healthy individuals. In some embodiments, the composition includes a strain derived from a single individual. In some embodiments, the composition includes strains derived from multiple individuals. In some embodiments, the bacterial strain is obtained from multiple individuals, isolated and grown individually. Individually grown bacterial compositions can then be combined to provide the composition of the present disclosure. It should be understood that the origin of the bacterial strains of the compositions provided herein is not limited to the human microbiome from healthy individuals. In some embodiments, the bacterial strain is derived from a human having a microbiota disrupted by an intestinal flora. In some embodiments, the bacterial strain is derived from a non-human animal or environment (eg, soil or surface water). In some embodiments, the combination of bacterial strains provided herein is derived from multiple sources (eg, human and non-human animals).

在本文提供的組成物之一些實施例中，組成物包括一或多種厭氧菌。在本文提供的組成物之一些實施例中，組成物僅包括厭氧菌。在本文提供的組成物之一些實施例中，組成物包括一或多種兼性厭氧菌。在本文提供的組成物之一些實施例中，組成物僅包括兼性厭氧菌。在本文提供的組成物之一些實施例中，組成物包括一或多種專性厭氧菌。在本文提供的組成物之一些實施例中，組成物僅包括專性厭氧菌。In some embodiments of the composition provided herein, the composition includes one or more anaerobic bacteria. In some embodiments of the composition provided herein, the composition includes only anaerobic bacteria. In some embodiments of the compositions provided herein, the composition includes one or more facultative anaerobes. In some embodiments of the composition provided herein, the composition includes only facultative anaerobic bacteria. In some embodiments of the compositions provided herein, the composition includes one or more obligate anaerobes. In some embodiments of the composition provided herein, the composition includes only obligate anaerobes.

在本文提供的組成物之一些實施例中，細菌菌株中之一或多者不具有抗生素抗性基因。在本文提供的組成物之一些實施例中，細菌菌株不具有使得細菌菌株對萬古黴素有抗性的抗生素抗性基因。In some embodiments of the compositions provided herein, one or more of the bacterial strains do not have an antibiotic resistance gene. In some embodiments of the compositions provided herein, the bacterial strain does not have an antibiotic resistance gene that renders the bacterial strain resistant to vancomycin.

在本文提供的組成物之一些實施例中，組成物不包括對一或多種抗生素有抗性的細菌菌株。應瞭解，可能合乎需要的是具有在投與之後自身體移除本文提供的細菌組成物之機制。一種此機制係藉由抗生素治療移除細菌組成物。因此，在一些實施例中，組成物不包括對一或多種抗生素有抗性的細菌菌株。在一些實施例中，組成物不包括對選自由以下各項組成之群的一或多種抗生素有抗性的細菌菌株：青黴素、苄基青黴素、安比西林、舒巴坦、安莫西林、克拉維酸、他唑巴坦、哌拉西林、西福每他唑、萬古黴素、亞胺培、美洛培南、甲硝噠唑及氯林絲菌素。在一些實施例中，組成物不包括對萬古黴素有抗性的細菌菌株。In some embodiments of the composition provided herein, the composition does not include a bacterial strain that is resistant to one or more antibiotics. It should be understood that it may be desirable to have a mechanism to remove the bacterial composition provided herein itself after administration. One such mechanism is the removal of bacterial constituents by antibiotic treatment. Therefore, in some embodiments, the composition does not include a bacterial strain that is resistant to one or more antibiotics. In some embodiments, the composition does not include a bacterial strain that is resistant to one or more antibiotics selected from the group consisting of: penicillin, benzyl penicillin, ampicillin, sulbactam, amoxicillin, clavidi Acid, tazobactam, piperacillin, sifametazol, vancomycin, imipenem, meropenem, metronidazole, and clindamycin. In some embodiments, the composition does not include a bacterial strain that is resistant to vancomycin.

在一些實施例中，組成物包括對在人類中有效的至少四種抗生素敏感的細菌菌株。在一些實施例中，組成物包括對在人類中有效的至少三種抗生素敏感的細菌菌株。在一些實施例中，組成物包括對在人類中有效的至少兩種抗生素敏感的細菌菌株。在一些實施例中，組成物包括對在人類中有效的至少一種抗生素敏感的細菌菌株。在一些實施例中，組成物僅包括對在人類中有效的至少四種抗生素敏感的細菌菌株。在一些實施例中，組成物僅包括對在人類中有效的至少三種抗生素敏感的細菌菌株。在一些實施例中，組成物僅包括對在人類中有效的至少兩種抗生素敏感的細菌菌株。在一些實施例中，組成物包括對在人類中有效的至少一種抗生素敏感的細菌菌株。(如本文所使用的「在人類中有效的抗生素」為已成功地用於治療人類之細菌感染的抗生素)。In some embodiments, the composition includes a bacterial strain that is sensitive to at least four antibiotics that are effective in humans. In some embodiments, the composition includes a bacterial strain that is sensitive to at least three antibiotics that are effective in humans. In some embodiments, the composition includes a bacterial strain that is sensitive to at least two antibiotics that are effective in humans. In some embodiments, the composition includes a bacterial strain that is sensitive to at least one antibiotic that is effective in humans. In some embodiments, the composition includes only bacterial strains that are sensitive to at least four antibiotics that are effective in humans. In some embodiments, the composition includes only bacterial strains that are sensitive to at least three antibiotics that are effective in humans. In some embodiments, the composition includes only bacterial strains that are sensitive to at least two antibiotics that are effective in humans. In some embodiments, the composition includes a bacterial strain that is sensitive to at least one antibiotic that is effective in humans. ("Antibiotics that are effective in humans" as used herein are antibiotics that have been successfully used to treat bacterial infections in humans).

在本文提供的組成物之一些實施例中，細菌菌株中之一或多者為孢子形成劑。在本文提供的組成物之一些實施例中，細菌菌株中之一或多者係呈孢子形式。在本文提供的組成物之一些實施例中，細菌菌株中之一或多者為非孢子形成劑。In some embodiments of the compositions provided herein, one or more of the bacterial strains are spore-forming agents. In some embodiments of the compositions provided herein, one or more of the bacterial strains are in the form of spores. In some embodiments of the compositions provided herein, one or more of the bacterial strains are non-spore-forming agents.

在一些實施例中，本文描述的組成物包含形成孢子及不形成孢子之細菌菌株。在一些實施例中，本文描述的組成物包含形成孢子之細菌菌株。在一些實施例中，本文描述的組成物僅包含形成孢子之細菌菌株。在一些實施例中，本文描述的組成物僅包含不形成孢子之細菌菌株。形成孢子之細菌可成孢子形式(亦即，為孢子)或呈營養形式(亦即，為營養細胞)。呈孢子形式的情況下，細菌通常對環境條件更有抗性，該等環境條件諸如熱、酸、輻射、氧、化學物質及抗生素。對比而言，呈營養狀態或主動生長狀態的情況下，相較於呈孢子形式的情況下，細菌對此等環境條件更敏感。一般而言，細菌孢子能夠在適當的條件下自孢子形式萌芽成營養/主動生長狀態。例如，呈孢子格式之細菌可在其引入腸中時萌芽。In some embodiments, the compositions described herein include spore-forming and non-spore-forming bacterial strains. In some embodiments, a composition described herein comprises a spore-forming bacterial strain. In some embodiments, the compositions described herein comprise only spore-forming bacterial strains. In some embodiments, the compositions described herein include only bacterial strains that do not form spores. Spore-forming bacteria can be in the form of spores (ie, spores) or in vegetative form (ie, vegetative cells). In the form of spores, bacteria are generally more resistant to environmental conditions such as heat, acids, radiation, oxygen, chemicals and antibiotics. In contrast, in the case of vegetative or active growth, bacteria are more sensitive to these environmental conditions than in the case of spores. In general, bacterial spores are able to sprout from spore form into a vegetative / active growth state under appropriate conditions. For example, bacteria in a spore format can sprout when they are introduced into the intestine.

在一些實施例中，組成物中之細菌菌株之至少一者(例如，1、2、3、4、5或更多者)為孢子形成劑。在一些實施例中，組成物中之細菌菌株之至少一者(例如，1、2、3、4、5或更多者)係呈孢子形式。在一些實施例中，組成物中之細菌菌株之至少一者(例如，1、2、3、4、5或更多者)為非孢子形成劑。在一些實施例中，組成物中之細菌菌株之至少一者(例如，1、2、3、4、5或更多者)係呈營養形式(如上文論述，形成孢子之細菌亦可呈營養形式)。在一些實施例中，組成物中之細菌菌株之至少一者(例如，1、2、3、4、5或更多者)係呈孢子形式且組成物中之細菌菌株之至少一者(例如，1、2、3、4、5或更多者)係呈營養形式。在一些實施例中，至少一種細菌菌株係視為能夠形成孢子(亦即，孢子形成劑)但以營養形式存在於組成物中。在一些實施例中，視為能夠形成孢子的至少一種細菌菌株係以孢子形式及營養形式兩者存在於組成物中。In some embodiments, at least one of the bacterial strains in the composition (eg, one, two, three, four, five, or more) is a spore forming agent. In some embodiments, at least one of the bacterial strains in the composition (eg, one, two, three, four, five, or more) is in the form of a spore. In some embodiments, at least one of the bacterial strains in the composition (eg, one, two, three, four, five, or more) is a non-spore-forming agent. In some embodiments, at least one of the bacterial strains in the composition (e.g., 1, 2, 3, 4, 5, or more) is in a nutritional form (as discussed above, the spore-forming bacteria can also be nutritional form). In some embodiments, at least one of the bacterial strains in the composition (e.g., 1, 2, 3, 4, 5, or more) is in the form of a spore and at least one of the bacterial strains in the composition (e.g., , 1, 2, 3, 4, 5 or more) are in nutritional form. In some embodiments, at least one bacterial strain is considered to be capable of forming spores (ie, spore-forming agents) but is present in the composition in a nutritional form. In some embodiments, at least one bacterial strain considered to be capable of forming spores is present in the composition in both a spore form and a nutritional form.

設想本文提供的組成物之細菌菌株為活的且將在其達到標靶區域(例如，腸)時為活的。細菌孢子在此方面係視為活的。在一些實施例中，作為孢子投與的細菌可在標靶區域(例如，腸)中萌芽。應進一步瞭解，並非所有細菌為活的且組成物可包括不為活的的百分比(例如，以重量計)。另外，在一些實施例中，組成物包括在投與時或在組成物達到標靶區域(例如，腸)時不為活的的細菌菌株。設想非活細菌可仍藉由提供用於組成物中之其他細菌菌株的一些養分及代謝物而為有用的。It is envisaged that the bacterial strain of the composition provided herein is alive and will be alive when it reaches a target area (eg, intestine). Bacterial spores are considered alive in this regard. In some embodiments, the bacteria administered as spores can germinate in a target area (eg, the intestine). It should be further understood that not all bacteria are viable and the composition may include a percentage (e.g., by weight) that is not viable. In addition, in some embodiments, the composition includes a bacterial strain that is not viable when administered or when the composition reaches a target area (e.g., intestine). It is contemplated that non-living bacteria may still be useful by providing some nutrients and metabolites for other bacterial strains in the composition.

在一些實施例中，在本文提供的任何組成物中，細菌菌株為純化的。在一些實施例中，在本文提供的任何組成物中，細菌菌株為分離的。本文描述的任何細菌菌株可例如自諸如培養物或微生物群樣本(例如，糞便物)之來源分離及/或純化。用於本文提供的組成物中之細菌菌株通常係自健康個體之微生物群分離。然而，細菌菌株亦可自視為不健康的個體分離。在一些實施例中，組成物包括來源於多個個體之菌株。如本文所使用，術語「分離」細菌係已自一或多種非所欲組分(諸如另一細菌或細菌菌株)、生長培養基之一或多種組分及/或樣本(諸如糞便樣本)之一或多種組分分離。在一些實施例中，細菌係實質上自一來源分離以使得不偵測該來源之其他組分。亦如本文所使用的，術語「純化」係指細菌菌株或組成物，其已與一或多種諸如污染物之組分分離。在一些實施例中，細菌菌株實質上不含污染物。在一些實施例中，組成物之一或多種細菌菌株可獨立地自產生於及/或存在於含有細菌菌株之培養物或樣本中的一或多種其他細菌純化。在一些實施例中，細菌菌株係自一樣本分離或純化且隨後在用於細菌複製之適當條件下、例如在厭氧培養條件下培養。在用於細菌複製之適當條件下生長的細菌可隨後自其生長所在之培養物分離/純化。In some embodiments, in any of the compositions provided herein, the bacterial strain is purified. In some embodiments, in any of the compositions provided herein, the bacterial strain is isolated. Any bacterial strain described herein can be isolated and / or purified, for example, from a source such as a culture or microbiome sample (e.g., fecal matter). Bacterial strains used in the compositions provided herein are typically isolated from the microbiota of healthy individuals. However, bacterial strains can also be isolated from individuals considered unhealthy. In some embodiments, the composition includes strains derived from multiple individuals. As used herein, the term "isolated" bacteria is derived from one or more undesired components (such as another bacteria or bacterial strain), one or more components of a growth medium, and / or one of a sample (such as a stool sample). Or multiple components are separated. In some embodiments, the bacteria are substantially isolated from a source such that other components of the source are not detected. As also used herein, the term "purified" refers to a bacterial strain or composition that has been separated from one or more components such as contaminants. In some embodiments, the bacterial strain is substantially free of contaminants. In some embodiments, one or more bacterial strains of the composition can be independently purified from one or more other bacteria produced and / or present in a culture or sample containing the bacterial strain. In some embodiments, the bacterial strain is isolated or purified from a specimen and then cultured under appropriate conditions for bacterial replication, such as under anaerobic culture conditions. Bacteria grown under appropriate conditions for bacterial replication can then be isolated / purified from the culture in which they are grown.

在一個態樣中，本揭示內容提供具有獨特生物學性質之細菌菌株及細菌菌株之混合物。在本文提供的組成物之一些實施例中，組成物誘導CD8+ T細胞之增殖及/或累積。在一些實施例中，本文提供的組成物之細菌菌株可由於細菌菌株之間的協同作用來誘導CD8+ T細胞之增殖及/或累積。因此，在不限於一特定機制的情況下，在一些實施例中，本文提供的組成物之細菌菌株之組合在誘導CD8+ T細胞之增殖及/或累積中協同地作用，因為菌株之組合尤其適於產生代謝物及/或細胞信號，其刺激CD8+ T細胞之增殖及/或累積之誘導。細菌組成物可例如經由使用腸道(例如，結腸或盲腸)中之養分，及/或產生代謝物及/或細胞信號之代謝交互作用來照此進行，該等代謝物及/或細胞信號刺激CD8+ T細胞之增殖及/或累積之誘導。另外，在不限於一特定機制的情況下，在一些實施例中，本文提供的組成物之細菌菌株之組合在誘導CD8+ T細胞之增殖及/或累積中協同地作用，因為菌株之組合在於腸道(例如，結腸或盲腸)中植入特定小生境中為優異的，該特定小生境將導致誘導CD8+ T細胞之增殖及/或累積(例如，藉由提供有利的微環境)。在一些實施例中，本文提供的組成物之細菌菌株之組合在誘導CD8+ T細胞之增殖及/或累積中協同地作用，因為菌株之組合尤其良好適於產生代謝物及/或細胞信號，其刺激CD8+ T細胞之增殖及/或累積之誘導，且該組合良好適於植入特定小生境中，從而導致代謝物及/或細胞信號定域至標靶以供誘導CD8+ T細胞之增殖及/或累積。 疾病之治療 癌症In one aspect, the present disclosure provides bacterial strains and mixtures of bacterial strains with unique biological properties. In some embodiments of the composition provided herein, the composition induces proliferation and / or accumulation of CD8 + T cells. In some embodiments, bacterial strains of the compositions provided herein can induce the proliferation and / or accumulation of CD8 + T cells due to the synergy between the bacterial strains. Therefore, without being limited to a specific mechanism, in some embodiments, the combination of bacterial strains of the composition provided herein synergistically induces the proliferation and / or accumulation of CD8 + T cells because the combination of strains is particularly suitable In the production of metabolites and / or cellular signals, it stimulates the induction of proliferation and / or accumulation of CD8 + T cells. Bacterial compositions can be performed, for example, through the use of nutrients in the gut (e.g., colon or cecum), and / or metabolic interactions that produce metabolites and / or cellular signals that are stimulated by such metabolites and / or cellular signals Induction of CD8 + T cell proliferation and / or accumulation. In addition, without being limited to a specific mechanism, in some embodiments, the combination of bacterial strains of the composition provided herein synergistically induces the proliferation and / or accumulation of CD8 + T cells, because the combination of strains lies in the intestine The implantation in the tract (e.g., colon or cecum) in a particular niche is superior, which will result in the induction of proliferation and / or accumulation of CD8 + T cells (e.g., by providing a favorable microenvironment). In some embodiments, the combination of bacterial strains of the compositions provided herein act synergistically in inducing the proliferation and / or accumulation of CD8 + T cells, as the combination of strains is particularly well-suited for generating metabolites and / or cellular signals, which Stimulates the induction of proliferation and / or accumulation of CD8 + T cells, and the combination is well-suited for implantation in a specific niche, resulting in localization of metabolites and / or cell signals to targets for inducing CD8 + T cell proliferation and / Or cumulative. Disease Treatment Cancer

在一個態樣中，本揭示內容包括用於治療受試者之疾病的組成物及方法。在本文提供的方法之一些實施例中，受試者患有癌症。在一個態樣中，可根據本文提供的組成物及方法治療的癌症包括而不限於惡性腫瘤、神經膠質瘤、間皮瘤、黑素瘤、淋巴瘤、白血病、腺癌、乳癌、卵巢癌、子宮頸癌、神經膠質母細胞瘤、多發性骨髓瘤、前列腺癌、伯基特氏淋巴瘤、頭頸癌、結腸癌、結腸直腸癌、非小細胞肺癌、小細胞肺癌、食管癌、胃癌、胰腺癌、肝膽癌、膽囊癌、小腸癌、直腸癌、腎癌、膀胱癌、前列腺癌、陰莖癌、尿道癌、睾丸癌、陰道癌、子宮癌、甲狀腺癌、副甲狀腺癌、腎上腺癌、胰腺內分泌癌、類癌瘤癌、骨癌、皮膚癌、視網膜母細胞瘤、霍奇金氏淋巴瘤、非霍奇金氏淋巴瘤、卡波西氏肉瘤、多中心Castleman氏病、AIDS相關原發性滲出淋巴瘤、神經外胚層腫瘤或橫紋肌肉瘤。在本文提供的方法之一些實施例中，癌症為前列腺癌、膀胱癌、非小細胞肺癌、泌尿上皮細胞惡性腫瘤、黑素瘤或腎細胞惡性腫瘤。在本文提供的方法之一些實施例中，受試者經歷放射治療。In one aspect, the disclosure includes compositions and methods for treating a subject's disease. In some embodiments of the methods provided herein, the subject has cancer. In one aspect, cancers that can be treated according to the compositions and methods provided herein include, but are not limited to, malignant tumors, gliomas, mesothelioma, melanoma, lymphoma, leukemia, adenocarcinoma, breast cancer, ovarian cancer, Cervical cancer, glioblastoma, multiple myeloma, prostate cancer, Burkitt's lymphoma, head and neck cancer, colon cancer, colorectal cancer, non-small cell lung cancer, small cell lung cancer, esophageal cancer, gastric cancer, pancreas Cancer, hepatobiliary cancer, gallbladder cancer, small intestine cancer, rectal cancer, kidney cancer, bladder cancer, prostate cancer, penile cancer, urethral cancer, testicular cancer, vaginal cancer, uterine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, pancreatic endocrine Carcinoma, carcinoid tumor, bone cancer, skin cancer, retinoblastoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, Kaposi's sarcoma, multicenter Castleman's disease, AIDS-related primary Exudative lymphoma, neuroectodermal tumor, or rhabdomyosarcoma. In some embodiments of the methods provided herein, the cancer is prostate cancer, bladder cancer, non-small cell lung cancer, urinary epithelial cell malignancy, melanoma, or renal cell malignancy. In some embodiments of the methods provided herein, the subject undergoes radiation therapy.

在本文提供的方法之一些實施例中，方法進一步包括投與一或多種抗癌劑。在本文提供的方法之一些實施例中，抗癌劑為化療劑。在本文提供的方法之一些實施例中，抗癌劑為癌症免疫療法劑。In some embodiments of the methods provided herein, the method further comprises administering one or more anticancer agents. In some embodiments of the methods provided herein, the anticancer agent is a chemotherapeutic agent. In some embodiments of the methods provided herein, the anticancer agent is a cancer immunotherapy agent.

在本文提供的方法之一些實施例中，癌症免疫療法劑為免疫查核點抑制劑。在本文提供的方法之一些實施例中，免疫查核點抑制劑為PD-1抑制劑、PD-L-1抑制劑或CTLA-4抑制劑。在本文提供的方法之一些實施例中，免疫查核點抑制劑為PD-1抑制劑。在本文提供的方法之一些實施例中，免疫查核點抑制劑為CTLA-4抑制劑。In some embodiments of the methods provided herein, the cancer immunotherapy agent is an immune checkpoint inhibitor. In some embodiments of the methods provided herein, the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L-1 inhibitor, or a CTLA-4 inhibitor. In some embodiments of the methods provided herein, the immune checkpoint inhibitor is a PD-1 inhibitor. In some embodiments of the methods provided herein, the immune checkpoint inhibitor is a CTLA-4 inhibitor.

在本文提供的方法之一些實施例中，癌症免疫療法劑為起作用來增加受試者之免疫系統對癌細胞之反應的癌症疫苗。例如，癌症疫苗包括起作用來誘導或刺激針對帶有癌症抗原之細胞的免疫反應之癌症抗原。所誘導或刺激的免疫反應可包括抗體(體液)免疫反應及/或T細胞(細胞介導)免疫反應。CD8+ T細胞可分化成細胞毒性T細胞，其殺死帶有由CD8+ T細胞辨別的抗原之標靶細胞。CD8+ T細胞之誘導可因此增強對提供於癌症疫苗中之癌症抗原的免疫反應。In some embodiments of the methods provided herein, a cancer immunotherapy agent is a cancer vaccine that functions to increase the subject's immune system response to cancer cells. For example, cancer vaccines include cancer antigens that function to induce or stimulate an immune response against cells bearing the cancer antigen. The immune response induced or stimulated may include an antibody (humoral) immune response and / or a T-cell (cell-mediated) immune response. CD8 + T cells can differentiate into cytotoxic T cells, which kill target cells with antigens identified by CD8 + T cells. The induction of CD8 + T cells can thus enhance the immune response to cancer antigens provided in cancer vaccines.

在本文提供的方法之一些實施例中，癌症免疫療法劑為CAR-T治療性的。CAR-T細胞包括自患者取出的T細胞，該等T細胞經遺傳工程化來在其表面上產生嵌合抗原受體(chimeric antigen receptor；CAR)。CAR經工程化以辨別癌細胞上之特定抗原。在CAR-T細胞輸注至患者中之後，其辨別並殺死在其表面上表現特定抗原之癌細胞。CD8+ T細胞之誘導適用於提供用於轉化成CAR-T細胞之細胞。In some embodiments of the methods provided herein, the cancer immunotherapy agent is CAR-T therapeutic. CAR-T cells include T cells removed from a patient, and these T cells are genetically engineered to produce a chimeric antigen receptor (CAR) on their surface. CAR is engineered to identify specific antigens on cancer cells. After CAR-T cells are infused into a patient, they identify and kill cancer cells that express a specific antigen on their surface. The induction of CD8 + T cells is suitable for providing cells for transformation into CAR-T cells.

在本文提供的方法之一些實施例中，方法進一步包括投與一或多種細胞介素。在本文提供的方法之一些實施例中，細胞介素為IL-2、IL-15或IL-21。In some embodiments of the methods provided herein, the method further comprises administering one or more cytokines. In some embodiments of the methods provided herein, the interleukin is IL-2, IL-15 or IL-21.

在本文提供的方法之一些實施例中，方法進一步包括投與一或多種共激劑。在本文提供的方法之一些實施例中，共激劑為CD-28、OX-40、4-1BB或CD40抗體。In some embodiments of the methods provided herein, the method further comprises administering one or more co-stimulants. In some embodiments of the methods provided herein, the stimulant is a CD-28, OX-40, 4-1BB, or CD40 antibody.

在本文提供的方法之一些實施例中，方法進一步包括投與一或多種疫苗。在本文提供的方法之一些實施例中，疫苗為樹狀細胞疫苗。In some embodiments of the methods provided herein, the method further comprises administering one or more vaccines. In some embodiments of the methods provided herein, the vaccine is a dendritic cell vaccine.

在本文提供的方法之一些實施例中，方法進一步包括投與授受性細胞轉移療法。在本文提供的方法之一些實施例中，授受性細胞轉移療法為工程化T細胞受體或嵌合抗原受體之使用。In some embodiments of the methods provided herein, the method further comprises administering a recipient cell transfer therapy. In some embodiments of the methods provided herein, the adaptive cell transfer therapy is the use of an engineered T cell receptor or a chimeric antigen receptor.

在本文提供的組成物之一些實施例中，組成物進一步包含一或多種抗癌劑。在本文提供的組成物之一些實施例中，抗癌劑為化療劑。在本文提供的組成物之一些實施例中，抗癌劑為癌症免疫療法劑。在本文提供的組成物之一些實施例中，癌症免疫療法劑為免疫查核點抑制劑。在本文提供的組成物之一些實施例中，免疫查核點抑制劑為PD-1抑制劑、PD-L-1抑制劑或CTLA-4抑制劑。在本文提供的組成物之一些實施例中，免疫查核點抑制劑為PD-1抑制劑、PD-L-1抑制劑、CTLA-4抑制劑、IDO1抑制劑、LAG3抑制劑或TIM3抑制劑。在本文提供的組成物之一些實施例中，免疫查核點抑制劑為PD-1抑制劑。在一些實施例中，PD-1抑制劑為納武單抗。在一些實施例中，PD-1抑制劑為派姆單抗。在一些實施例中，PD-1抑制劑為匹地利珠單抗(pidiluzimab)。在本文提供的組成物之一些實施例中，免疫查核點抑制劑為PD-L-1抑制劑。在一些實施例中，PD-L-1抑制劑阿特珠單抗。在一些實施例中，PD-L-1抑制劑阿維魯單抗。在一些實施例中，PD-L-1抑制劑度伐魯單抗(durvalumab)。在本文提供的方法之一些實施例中，免疫查核點抑制劑為CTLA-4抑制劑。在一些實施例中，CTLA-4抑制劑為抗CTLA-4抗體。抗CTLA-4抗體之實例包括而不限於依匹單抗、曲美利單抗(tremelimumab；CP-675,206)、9H10、4F10及9D9。在一些實施例中，CTLA-4抑制劑為依匹單抗。在一些實施例中，CTLA-4抑制劑為曲美利單抗。應進一步瞭解，多種抗癌劑(例如，免疫查核點抑制劑)可包括在本文揭示的組成物及方法中。例如，在非限制性實例中，所揭示的組成物及方法包括PD-1抑制劑及CTLA-4抑制劑兩者。In some embodiments of the composition provided herein, the composition further comprises one or more anticancer agents. In some embodiments of the compositions provided herein, the anticancer agent is a chemotherapeutic agent. In some embodiments of the compositions provided herein, the anticancer agent is a cancer immunotherapy agent. In some embodiments of the compositions provided herein, the cancer immunotherapy agent is an immune checkpoint inhibitor. In some embodiments of the compositions provided herein, the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L-1 inhibitor, or a CTLA-4 inhibitor. In some embodiments of the compositions provided herein, the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L-1 inhibitor, a CTLA-4 inhibitor, an IDO1 inhibitor, a LAG3 inhibitor, or a TIM3 inhibitor. In some embodiments of the compositions provided herein, the immune checkpoint inhibitor is a PD-1 inhibitor. In some embodiments, the PD-1 inhibitor is nivolumab. In some embodiments, the PD-1 inhibitor is paimumab. In some embodiments, the PD-1 inhibitor is pidiluzimab. In some embodiments of the compositions provided herein, the immune checkpoint inhibitor is a PD-L-1 inhibitor. In some embodiments, the PD-L-1 inhibitor is atelizumab. In some embodiments, the PD-L-1 inhibitor is aviluzumab. In some embodiments, the PD-L-1 inhibitor durvalumab. In some embodiments of the methods provided herein, the immune checkpoint inhibitor is a CTLA-4 inhibitor. In some embodiments, the CTLA-4 inhibitor is an anti-CTLA-4 antibody. Examples of anti-CTLA-4 antibodies include, but are not limited to, epilimumab, tremelimumab (CP-675,206), 9H10, 4F10, and 9D9. In some embodiments, the CTLA-4 inhibitor is epilimumab. In some embodiments, the CTLA-4 inhibitor is trimmelizumab. It should be further understood that a variety of anticancer agents (eg, immune checkpoint inhibitors) may be included in the compositions and methods disclosed herein. For example, in non-limiting examples, the disclosed compositions and methods include both PD-1 inhibitors and CTLA-4 inhibitors.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌，以及PD-1抑制劑。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising Koala faecalis, Clostridium ulcerans, Bacteroides dorsii, Bacteroides monomorphum, Rare micrococcus, Paraprevotella xylaniphila, about Pseudomonas aeruginosa, Pseudomonas aeruginosa, Pseudomonas gordonii, Pseudomonas mycoides and Pseudomonas deerii, and PD-1 inhibitors.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌，以及PD-L-1抑制劑。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising Koala faecalis, Clostridium ulcerans, Bacteroides dorsii, Bacteroides monomorphum, Rare micrococcus, Paraprevotella xylaniphila, about Pseudomonas aeruginosa, Pseudomonas aeruginosa, Pseudomonas gordonii, Pseudomonas myxobacteria and Pseudomonas deerii, and PD-L-1 inhibitors.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌，以及CTLA-4抑制劑。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising Koala faecalis, Clostridium ulcerans, Bacteroides dorsii, Bacteroides monomorphum, Rare micrococcus, Paraprevotella xylaniphila, about Parabacillus spp., Allobacterium spp., Paragliobacter gordonii, Eumycobacterium myxesum and Paracoccus difficile, and CTLA-4 inhibitors.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株及PD-1抑制劑，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain and a PD-1 inhibitor, the bacterial strain comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株及PD-L-1抑制劑，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain and a PD-L-1 inhibitor, the bacterial strain comprising at least 97% homology to 16S rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO : 8, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株及CTLA-4抑制劑，該等細菌菌株包含與以下各項具有至少97%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain and a CTLA-4 inhibitor, the bacterial strain comprising 16S having at least 97% homology to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株及PD-1抑制劑，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain and a PD-1 inhibitor, the bacterial strain comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株及PD-L-1抑制劑，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain and a PD-L-1 inhibitor, the bacterial strain comprising at least 97% sequence identity to 16S rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO : 8, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株及CTLA-4抑制劑，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain and a CTLA-4 inhibitor, the bacterial strain comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 , SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株及PD-1抑制劑，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59，SEQ ID N0:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63及SEQ ID NO:64。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain and a PD-1 inhibitor, the bacterial strain comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61 , SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株及PD-L-1抑制劑，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59，SEQ ID N0:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63及SEQ ID NO:64。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain and a PD-L-1 inhibitor, the bacterial strain comprising at least 97% sequence identity to 16S rDNA sequence: SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO : 61, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64.

在一個態樣中，本揭示內容提供包含純化細菌混合物之組成物，該純化細菌混合物包含細菌菌株及CTLA-4抑制劑，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59，SEQ ID N0:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63及SEQ ID NO:64。In one aspect, the present disclosure provides a composition comprising a purified bacterial mixture comprising a bacterial strain and a CTLA-4 inhibitor, the bacterial strain comprising 16S having at least 97% sequence identity to rDNA sequence: SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61 , SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64.

在本文提供的組成物之一些實施例中，組成物進一步包括一或多種細胞介素。在本文提供的組成物之一些實施例中，細胞介素為IL-2、IL-15或IL-21。在本文提供的組成物之一些實施例中，組成物進一步包含一或多種共激劑。在本文提供的組成物之一些實施例中，共激劑為CD-28、OX-40、4-1BB或CD40抗體。In some embodiments of the composition provided herein, the composition further includes one or more cytokines. In some embodiments of the compositions provided herein, the interleukin is IL-2, IL-15, or IL-21. In some embodiments of the composition provided herein, the composition further comprises one or more co-stimulants. In some embodiments of the compositions provided herein, the stimulant is a CD-28, OX-40, 4-1BB, or CD40 antibody.

在本文提供的組成物之一些實施例中，組成物進一步包含一或多種疫苗。在本文提供的組成物之一些實施例中，疫苗為樹狀細胞疫苗。在本文提供的組成物之一些實施例中，組成物係與授受性細胞轉移療法組合。在本文提供的組成物之一些實施例中，授受性細胞轉移療法為工程化T細胞受體或嵌合抗原受體之使用。 傳染性疾病In some embodiments of the composition provided herein, the composition further comprises one or more vaccines. In some embodiments of the compositions provided herein, the vaccine is a dendritic cell vaccine. In some embodiments of the compositions provided herein, the composition is combined with an adaptive cell transfer therapy. In some embodiments of the compositions provided herein, the adaptive cell transfer therapy is the use of an engineered T cell receptor or a chimeric antigen receptor. Infectious disease

在一個態樣中，本揭示內容包括用於治療受試者之疾病的組成物及方法。在本文提供的方法之一些實施例中，受試者患有傳染性疾病。在本文提供的方法之一些實施例中，傳染性疾病為細菌感染、病毒感染、寄生蟲感染或真菌感染。在本文提供的方法之一些實施例中，傳染性疾病為病毒感染。在本文提供的方法之一些實施例中，病毒感染為HIV。在本文提供的方法之一些實施例中，感染為由肝炎病毒的感染。In one aspect, the disclosure includes compositions and methods for treating a subject's disease. In some embodiments of the methods provided herein, the subject has an infectious disease. In some embodiments of the methods provided herein, the infectious disease is a bacterial infection, a viral infection, a parasitic infection, or a fungal infection. In some embodiments of the methods provided herein, the infectious disease is a viral infection. In some embodiments of the methods provided herein, the viral infection is HIV. In some embodiments of the methods provided herein, the infection is an infection by a hepatitis virus.

在一些實施例中，本文提供的組成物可用作用於預防或治療諸如細菌感染、病毒感染、寄生蟲感染及真菌感染之傳染性疾病(部分地或完全地減少其不利效應)的醫藥組成物。In some embodiments, the compositions provided herein are useful as pharmaceutical compositions for preventing or treating infectious diseases such as bacterial, viral, parasitic, and fungal infections (partially or completely reducing their adverse effects).

可根據本文提供的方法治療的細菌感染包括但不限於綠膿桿菌(P. aeruginosa)、大腸桿菌、破傷風梭菌(C. tetani)、淋病奈瑟菌(N. gonorrhoeae)、肉毒桿菌(C. botulinum)、克留氏菌屬、沙雷氏菌屬、假單胞菌屬、洋蔥假單胞菌(P. cepacia)、不動細菌屬、表皮葡萄球菌(S. epidermis)、糞腸球菌、肺炎鏈球菌(S. pneumonias)、金黃色葡萄球菌(S. aureus)；變異鏈球菌(S. mutans)、嗜血桿菌屬、奈瑟氏球菌屬、腦膜炎奈瑟菌、擬桿菌屬、檸檬酸桿菌屬、布拉漢菌屬、沙門桿菌屬、志賀桿菌屬、化膿性鏈球菌(S. pyogenes)、變形菌屬、梭菌屬、丹毒菌屬、李氏菌屬、敗血性巴氏桿菌(Pasteurella multocida)、鏈桿菌屬、螺旋菌屬、富索螺旋菌屬(Fusospirocheta sp.)、梅毒螺旋體、疏螺旋體屬、放射菌類、黴漿菌屬、披衣菌屬、立克次體屬、螺旋體屬、伯氏疏螺旋體、軍團菌屬、分枝桿菌屬、尿漿菌屬、鏈黴菌屬、毛滴蟲屬、奇異變形菌(P. mirabilis)；霍亂弧菌、腸毒性大腸桿菌(enterotoxigenic Escherichia coli)、困難梭狀芽孢桿菌(Clostridium difficile)、傷寒沙氏桿菌(Salmonella typhi)、白喉桿菌(C. diphtheria)、麻瘋分枝桿菌(Mycobacterium leprae)、麻風結節分枝桿菌(Mycobacterium lepromatosi)。由耐藥物細菌所引起的可根據本文提供的方法治療的細菌感染包括但不限於產氣莢膜芽胞梭菌(Clostridium perfringens)；肉毒桿菌；Clostridium tributrycum；生孢梭菌(Clostridium sporogenes)；大腸桿菌；綠膿桿菌，諸如耐多藥物綠膿桿菌；耐萬古黴素腸道球菌(Vancomycin Resistant Enterococci；VRE)；耐碳青黴烯腸桿菌科(Carbapenem Resistant Enterobacteriaceae；CRE)；淋病奈瑟菌；不動細菌屬，耐多藥物不動細菌屬；彎曲桿菌屬；耐多藥物彎曲桿菌屬；念珠菌屬，耐氟康唑念珠菌屬，產生廣譜β-內醯胺酶(Extended spectrum beta-lactamase；ESBL)之腸桿菌科；沙門氏菌，鼠傷寒沙氏桿菌，耐藥物非傷寒沙門氏菌種；耐藥物傷寒沙氏桿菌；耐藥物志賀桿菌屬；金黃色葡萄球菌，諸如耐二甲苯青黴素金黃色葡萄球菌或耐萬古黴素金黃色葡萄球菌；耐藥物肺炎鏈球菌；耐藥物結核病；耐紅黴素A組鏈球菌；耐氯林絲菌素B組鏈球菌及其任何組合。Bacterial infections that can be treated according to the methods provided herein include, but are not limited to, P. aeruginosa, E. coli, C. tetani, N. gonorrhoeae, botulinum (C botulinum), Klebsiella, Serratia, Pseudomonas, P. cepacia, Acinetobacter, S. epidermis, Enterococcus faecalis, S. pneumonias, S. aureus; S. mutans, Haemophilus, Neisseria, Neisseria meningitidis, Bacteroides, lemon Acidobacterium, Brahima, Salmonella, Shigella, S. pyogenes, Proteus, Clostridium, Rhodotium, Listeria, Pasteurella septica (Pasteurella multocida), Streptomyces, Helicobacter, Fusospirocheta sp., Treponema pallidum, Borrelia, Radiobacterium, Mycelium, Chlamydia, Rickettsia, Borrelia, Borrelia burgdorferi, Legionella, Mycobacterium, Uroplasma, Streptomyces, Trichomonas, P. mirabilis; Vibrio cholerae, enterotoxigenic Escherichia coli, Clostridium difficile, Salmonella typhi C. diphtheria, Mycobacterium leprae, Mycobacterium lepromatosi. Bacterial infections caused by drug-resistant bacteria that can be treated according to the methods provided herein include, but are not limited to Clostridium perfringens; Botox; Clostridium tributrycum; Clostridium sporogenes; Large intestine Bacillus; Pseudomonas aeruginosa, such as multidrug-resistant Pseudomonas aeruginosa; Vancomycin Resistant Enterococci (VRE); Carbapenem Resistant Enterobacteriaceae (CRE); Neisseria gonorrhoeae; immobile Bacterium, Multidrug-resistant Bacterium; Campylobacter; Multidrug-resistant Campylobacter; Candida, Fluconazole-resistant Candida, producing Extended spectrum beta-lactamase (ESBL) Enterobacteriaceae; Salmonella, Salmonella typhimurium, drug-resistant non-typhoid Salmonella species; drug-resistant Salmonella typhimurium; drug-resistant Shigella; staphylococcus aureus, such as xylene toxin-resistant S. aureus Vancomycin Staphylococcus aureus; drug-resistant Streptococcus pneumoniae; drug-resistant tuberculosis; erythromycin-resistant group A streptococci ; Chlorine-resistant Streptococcus Group B avermectin Lin Si and any combination thereof.

可根據本文提供的方法治療的病毒感染包括但不限於小核醣核酸病毒屬、杯狀病毒科、披膜病毒科、黃病毒科、冠狀病毒科、炮彈病毒科、絲狀病毒科、副黏液病毒科、正黏液病毒科、布尼亞病毒科、沙狀病毒科、呼腸孤病毒科、反轉錄病毒科、肝病毒科、細小病毒科、乳多瘤病毒科、腺病毒科、皰疹病毒科、痘病毒科、輪狀病毒、副流感病毒、流感病毒A及B、肝炎病毒、梅毒、HIV、狂犬病病毒、艾司坦-巴爾病毒及單純性皰疹病毒。Viral infections that can be treated according to the methods provided herein include, but are not limited to, Picornaviridae, Caliciviridae, Mantleviridae, Flaviviridae, Coronaviridae, Cannoniviridae, Filaviridae, Paramyxovirus Family, Orthomyxoviridae, Bunyaviridae, Sarnaviridae, Reoviridae, Retroviridae, Liverviridae, Parvoviridae, Papillomaviridae, Adenoviridae, Herpesvirus Family, poxviridae, rotavirus, parainfluenza virus, influenza viruses A and B, hepatitis virus, syphilis, HIV, rabies virus, este-bar virus and herpes simplex virus.

可根據本文提供的方法治療的病毒感染包括但不限於惡性瘧原蟲(Plasmodium falciparum)、間日瘧原蟲(P. vivax)、蛋形瘧原蟲(P. ovale)、三日瘧原蟲(P. malaria)、弓漿蟲(Toxoplasma gondii)、墨西哥利什曼原蟲(Leishmania mexicana)、熱帶利什曼原蟲(L. tropica)、主要利什曼原蟲(L. major)、衣索比亞利什曼原蟲(L. aethiopica)、杜氏利什曼原蟲(L. donovani)、克氏錐蟲(Trypanosoma cruzi)、布氏錐蟲(T. brucei)、曼森氏住血吸蟲(Schistosoma mansoni)、埃及血吸蟲(S. haematobium)、日本血吸蟲(S. japonium)、旋毛蟲(Trichinella spiralis)、潘氏絲狀蟲(Wuchereria bancrofti)、馬來血絲蟲(Brugia malayli)、溶組織內阿米巴(Entamoeba histolytica)、蟯蟲(Enterobius vermiculoarus)、有鉤絛蟲(Taenia solium)、牛肉絛蟲(T. saginata)、陰道滴蟲(Trichomonas vaginatis)、人毛滴蟲(T. hominis)、口腔鞭毛滴蟲(T. tenax)；梨形鞭毛蟲(Giardia lamblia)、小隱孢子蟲(Cryptosporidium parvum)、卡氏肺囊蟲(Pneumocytis carinii)、牛焦蟲(Babesia bovis)、分岐焦蟲(B. divergens)、小鼠焦蟲(B. microti)、貝氏球蟲(Isospore belli)、L hominis、雙核阿米巴(Dientamoeba jragiles)、人蟠尾絲蟲(Onchocerca volvulus)、人蛔蟲(Ascaris lumbricoides)、美洲鉤蟲(Necator americanis)、十二指腸鉤蟲(Ancylostoma duodenale)、糞小桿線蟲(Strongyloides stercoralis)、菲律賓毛線蟲(Capillaria philippinensis)、廣東血線蟲(Angiostrongylus cantonensis)、微小包膜絛蟲(Hymenolepis nana)、廣節裂頭絛蟲(Diphyllobothrium latum)、顆粒性包生絛蟲(Echinococcus granulosus)、細粒棘球絛蟲(E. multilocularis)、衛氏肺吸蟲(Paragonimus westermani)、卡氏肺吸蟲(P. caliensis)、中華肝吸蟲(Chlonorchis sinensis)、貓肝吸蟲(Opisthorchis felineas)、泰國肝吸蟲(G. Viverini)、牛羊肝吸蟲(Fasciola hepatica)、人疥蟎(Sarcoptes scabiei)、人蝨(Pediculus humanus)、陰虱(Phthirius pubis)及人類馬蠅。Viral infections that can be treated according to the methods provided herein include, but are not limited to, Plasmodium falciparum, P. vivax, P. ovale, P. ovale, and Plasmodium falciparum (P. malaria), Toxoplasma gondii, Leishmania mexicana, L. tropica, L. major, clothing L. aethiopica, L. donovani, Trypanosoma cruzi, T. brucei, Schistosoma mansoni (Schistosoma mansoni), S. haematobium, S. japonium, Trichinella spiralis, Wuchereria bancrofti, Brugia malayli, lyso-tissue Entamoeba histolytica, Enterobius vermiculoarus, Taenia solium, T. saginata, Trichomonas vaginatis, T. hominis, Oral flagellates (T. tenax); Giardia lamblia, Cryptosp oridium parvum), Pneumocytis carinii, Babesia bovis, B. divergens, B. microti, Isospore belli, L hominis, Dientamoeba jragiles, Onchocerca volvulus, Ascaris lumbricoides, Necator americanis, Ancylostoma duodenale, Strongyloides stercoralis ), Capillaria philippinensis, Angiostrongylus cantonensis, Hymenolepis nana, Diphyllobothrium latum, Echinococcus granulosus, Echinococcus granulosus E. multilocularis, Paragonimus westermani, P. caliensis, Chlonorchis sinensis, Opisthorchis felineas, Thai liver fluke G. Viverini, Fasciola hepatica, Sarcopses scabiei, Pediculus humanus, Phthirius pubis, and humans Fly.

可根據本文提供的方法治療的真菌感染包括但不限於新型隱球菌(Cryptococcus neoformans)、皮炎芽生菌(Blastomyces dermatitidis)、Aiellomyces dermatitidis、莢膜組織胞漿菌(Histoplasfria capsulatum)、粗球孢子菌(Coccidioides immitis)、念珠菌種(Candida species)(包括白色念珠菌(C. albicans)、熱帶念珠菌(C. tropicalis)、近平滑念珠菌(C. parapsilosis)、季也蒙念珠菌(C. guilliermondii)及克魯斯念珠菌(C. krusei))、麴菌種(Aspergillus species)(包括薰煙色麴菌(A. fumigatus)、黃色麴菌(A.flavus)、黑色麴菌(A. niger))、酒麴菌種(Rhizopus species)、根黏菌種(Rhizomucor species)、小克銀漢黴種(Cunninghammella species)、Apophysomyces種(包括A. saksenaea、A. mucor及A. absidia)、申克氏絲孢子菌(Sporothrix schenckii)、巴西副球孢子菌(Paracoccidioides brasiliensis)、波氏假性黴樣菌(Pseudallescheria boydii)、光滑球擬酵母(Torulopsis glabrata)；及皮癬菌種(Dermatophyres species)。Fungal infections that can be treated according to the methods provided herein include, but are not limited to, Cryptococcus neoformans, Blastomyces dermatitidis, Aiellomyces dermatitidis, Histoplasfria capsulatum, Coccidioides immitis), Candida species (including C. albicans, C. tropicalis, C. parapsilosis, C. guilliermondii) And C. krusei), Aspergillus species (including A. fumigatus, A. flavus, A. niger) ), Rhizopus species, Rhizomocor species, Cunninghammella species, Apophysomyces species (including A. saksenaea, A. mucor and A. absidia), Schenck Sporothrix schenckii, Paracoccidioides brasiliensis, Pseudallescheria boydii, Torulopsis glabrata, and Dermatophyr es species).

在一個態樣中，本揭示內容提供包含本文提供的任何組成物及抗原的疫苗。在本文提供的疫苗之一些實施例中，抗原為HIV抗原。在本文提供的疫苗之一些實施例中，抗原為肝炎抗原。在一些實施例中，細菌組成物係作為與抗原材料組合之佐劑投與。抗原材料可包括蛋白質包衣、蛋白質核心或功能蛋白質及病原體或完整病原體(活的、死的、鈍化的或減毒的)之肽之一或多個部分，或可包含一個或複數個癌症抗原決定基或癌症抗原。抗原材料可與細菌組成物共同投與，在該細菌組成物之前或之後投與。細菌組成物亦可與諸如以下各項之現存黏膜疫苗一起投與：流感疫苗(例如，來自Medlmmune之FluMist或來自印度血清學會之NASOVAC)、輪狀病毒疫苗(例如，來自Merck之RotaTeq或來自GlaxoSmithKline之Rotarix)、傷寒疫苗(例如，來自Crucell之Vivotif、Ty21A)、霍亂疫苗(例如，來自Crucell之Orochol、來自Shantha Biotechnics之Shanchol)、旅行者之腹瀉疫苗(例如，來自Crucell之Dukoral)；及與以下各項之抗原一起投與：活減毒流感A病毒HI菌株、活減毒流感A病毒H3菌株、流感B病毒、活減毒H1N1流感病毒(豬流感)、活減毒輪狀病毒、單價及多價脊髓灰白質病毒、活減毒傷寒沙氏桿菌、缺乏霍亂毒素次單元A之活重組霍亂弧菌、具有或不具有霍亂毒素亞基B之完整殺死的霍亂弧菌01經典及El Tor生物型、癌症抗原、癌症抗原決定基及其組合。 自體免疫疾病或過敏性疾病In one aspect, the disclosure provides a vaccine comprising any of the compositions and antigens provided herein. In some embodiments of the vaccines provided herein, the antigen is an HIV antigen. In some embodiments of the vaccines provided herein, the antigen is a hepatitis antigen. In some embodiments, the bacterial composition is administered as an adjuvant in combination with an antigenic material. The antigenic material may include a protein coating, a protein core or functional protein, and one or more portions of a peptide of a pathogen or an intact pathogen (live, dead, inactivated, or attenuated), or may include one or more cancer antigens Determinant or cancer antigen. The antigenic material may be co-administered with the bacterial composition, either before or after the bacterial composition. Bacterial compositions can also be administered with existing mucosal vaccines such as: influenza vaccines (e.g. FluMist from Medlmmune or NASOVAC from the Indian Serological Society), rotavirus vaccines (e.g. RotaTeq from Merck or GlaxoSmithKline Rotarix), typhoid vaccine (e.g., Vivotif, Ty21A from Crucell), cholera vaccine (e.g., Orochol from Crucell, Shanchol from Shantha Biotechnics), traveler's diarrhea vaccine (e.g., Ducellal from Crucell); and The following antigens are administered together: live attenuated influenza A virus HI strain, live attenuated influenza A virus H3 strain, influenza B virus, live attenuated H1N1 influenza virus (swine flu), live attenuated rotavirus, unit price And polyvalent poliovirus, live attenuated Salmonella typhi, live recombinant Vibrio cholerae lacking cholera toxin subunit A, and fully killed Vibrio cholerae 01 with and without cholera toxin subunit B Tor biotype, cancer antigen, cancer epitope, and combinations thereof. Autoimmune disease or allergic disease

在一個態樣中，本揭示內容包括用於治療受試者之疾病的組成物及方法。在本文提供的方法之一些實施例中，受試者患有自體免疫疾病或過敏性疾病。In one aspect, the disclosure includes compositions and methods for treating a subject's disease. In some embodiments of the methods provided herein, the subject has an autoimmune disease or an allergic disease.

本揭示內容之組成物及方法可用於預防或治療自體免疫疾病及過敏性疾病。可治療的自體免疫疾病包括但不限於炎症性腸病、全身性紅斑狼瘡、類風濕性關節炎、多發性硬化或橋本氏病。可治療的過敏性疾病包括但不限於食物過敏、花粉病或哮喘。The composition and method of the present disclosure can be used to prevent or treat autoimmune diseases and allergic diseases. Treatable autoimmune diseases include, but are not limited to, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, or Hashimoto's disease. Allergic diseases that can be treated include, but are not limited to, food allergies, hay fever or asthma.

可根據本文提供的方法及組成物治療的自體免疫及過敏性疾病之另外實例包括而不限於器官移植之排斥，諸如炎症性腸病(inflammatory bowel disease；IBD)、潰瘍性結腸炎、克隆氏病、口瘡、自體免疫關節炎、類風濕性關節炎、I型糖尿病、多發性硬化、骨髓移植之後的移植物與宿主疾病、骨關節炎、少年慢性關節炎、來母關節炎、牛皮癬性關節炎、反應性關節炎、脊椎關節炎、全身性紅斑狼瘡、胰島素依賴型糖尿病、甲狀腺炎、哮喘、牛皮癬、皮炎硬皮病、異位性皮膚炎、移植物抗宿主病、與器官移植相關聯的急性或慢性免疫疾病、類肉瘤病、動脈粥樣硬化、散播性血管內凝血、Kawasaki氏病、葛瑞夫茲氏病、腎病徵候群、慢性疲勞症候群、華格納氏肉芽病、Henoch-Schoenlejn紫癜、腎之顯微多發性血管炎、慢性活動性肝炎、眼色素層炎、敗血性休克、毒性休克徵候群、敗血症候群、惡病體質、後天免疫不全症候群、急性橫貫性脊髓炎、亨爾頓氏舞蹈病、帕金森氏症、阿茲海默症、中風、原發性膽道性肝硬化症、溶血性貧血、多腺體缺陷I型症候群及多腺體缺陷II型症候群、施密特氏症候群、成人(急性)呼吸窘迫症候群、禿髮、斑禿、血清陰性關節炎、關節炎、Reiter氏病、乾癬性關節炎、披衣菌屬、耶氏桿菌及沙門氏菌相關聯之關節炎、脊椎崩解關節炎、粥瘤性疾病/動脈硬化症、過敏性結腸炎、異位性過敏、諸如花生過敏、樹堅果過敏、蛋過敏、牛奶過敏、大豆過敏、小麥過敏、海鮮過敏、貝介類過敏或芝麻籽過敏之食物過敏、自體免疫水皰病、尋常性天皰瘡、落葉性天皰瘡、類天皰瘡、線性IgA疾病、自體免疫溶血性貧血病、Coomb氏陽性溶血性貧血病、後天惡性貧血、少年惡性貧血、肌痛性腦炎/皇家自由疾病、慢性黏膜皮膚念珠菌病、巨大細胞動脈炎、原發性硬化性肝炎、隱原性自體免疫肝炎、後天免疫不全疾病症候群、後天免疫不全相關疾病、C型肝炎、普通變異型免疫缺陷(普通變異型咖瑪免疫球蛋白過低症)、擴張性心肌病、纖維性肺疾病、隱源性致纖維性肺泡炎、炎症後間質性肺疾病、間質性肺炎、結締組織疾病相關聯之間質性肺病、混合結締組織疾病相關聯之肺病、全身性硬化相關聯之間質性肺病、類風濕性關節炎相關聯之間質性肺病、全身性紅斑狼瘡相關聯之肺病、皮肌炎/多發性肌炎相關聯之肺病、休格倫氏病相關聯之肺病、關節黏連性脊椎炎相關聯之肺病、血管瀰漫性肺病、含鐵血紅素沉積症相關聯之肺病、藥物誘導之間質性肺病、放射性纖維化、閉塞性小枝氣管炎、慢性嗜伊紅性白血球肺炎、淋巴球浸潤性肺病、感染後間質性肺病、痛風性關節炎、自體免疫肝炎、1型自體免疫肝炎(經典自體免疫或類狼瘡性肝炎)、2型自體免疫肝炎(抗LKM抗體肝炎)、自體免疫介導的低血糖、伴有黑棘皮病之B型胰島素抗性、副甲狀腺低能症、與器官移植相關聯的急性免疫疾病、與器官移植相關聯的慢性免疫疾病、非炎性骨關節病、原發性硬化性膽管炎、特發性白血球減少症、自體免疫嗜中性白血球減少症、腎病NOS、腎絲球腎炎、腎之顯微多發性血管炎、盤形紅斑狼瘡、特發性或NOS之男性不育症、精液自體免疫症、多發性硬化(所有子型)、胰島素依賴型糖尿病、交感性眼炎、繼發於結締組織疾病之肺動脈高血壓、古巴士德氏症候群、結節性多動脈炎之肺部表現、急性類風濕性發燒、類風濕性脊椎炎、Still氏病、全身性硬化、Takayasu氏病/動脈炎、自體免疫血小板減少症、特發性血小板減少症、自體免疫性甲狀腺病、甲狀腺高能症、甲狀腺腫性自體免疫甲狀腺低能症(橋本氏病)、萎縮性自體免疫甲狀腺低能症、原發性黏液水腫、晶狀體源性眼色素層炎、原發性脈管炎、白斑病、過敏性鼻炎(花粉過敏)、重度過敏、寵物過敏、乳汁過敏、藥物過敏、過敏性鼻結膜炎、嗜伊紅性食道炎、嗜伊紅性白血球增多症候群、嗜伊紅性腸胃炎、皮膚紅斑狼瘡、嗜伊紅性食道炎、嗜伊紅性白血球增多症候群、嗜伊紅性腸胃炎及腹瀉。Additional examples of autoimmune and allergic diseases that can be treated according to the methods and compositions provided herein include, without limitation, rejection of organ transplants, such as inflammatory bowel disease (IBD), ulcerative colitis, Crohn's Disease, aphtha, autoimmune arthritis, rheumatoid arthritis, type I diabetes, multiple sclerosis, graft and host disease after bone marrow transplantation, osteoarthritis, juvenile chronic arthritis, maternal arthritis, psoriasis Arthritis, reactive arthritis, spinal arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, thyroiditis, asthma, psoriasis, dermatitis scleroderma, atopic dermatitis, graft versus host disease, and organ transplantation related Associated acute or chronic immune disease, sarcomatoid disease, atherosclerosis, disseminated intravascular coagulation, Kawasaki's disease, Graves' disease, nephrotic syndrome, chronic fatigue syndrome, Wagner's granulomatosis, Henoch-Schoenlejn Purpura, microscopic polyangiitis of the kidney, chronic active hepatitis, uveitis, septic shock, toxic shock Syndrome, sepsis syndrome, malignant constitution, acquired immune deficiency syndrome, acute transverse myelitis, Henry's chorea, Parkinson's disease, Alzheimer's disease, stroke, primary biliary cirrhosis Disease, hemolytic anemia, polyglandular deficiency type I syndrome and polyglandular deficiency type II syndrome, Schmidt syndrome, adult (acute) respiratory distress syndrome, baldness, alopecia areata, serum negative arthritis, arthritis, Reiter 'S disease, psoriasis arthritis, Chlamydia, Yersinia and Salmonella-associated arthritis, spinal disintegrating arthritis, atheromatous disease / arteriosclerosis, allergic colitis, atopic allergy, such as Peanut allergy, tree nut allergy, egg allergy, milk allergy, soy allergy, wheat allergy, seafood allergy, shellfish allergy or sesame seed allergy food allergy, autoimmune vesicular disease, pemphigus vulgaris, deciduous pemphigus Sores, pemphigoid, linear IgA disease, autoimmune hemolytic anemia, Coomb's positive hemolytic anemia, acquired malignant anemia, juvenile malignant anemia, myalgia encephalitis / royal freedom Disease, chronic mucosal skin candidiasis, giant cell arteritis, primary sclerosing hepatitis, cryptogenic autoimmune hepatitis, acquired immune deficiency disease syndrome, acquired immune deficiency related disease, hepatitis C, common variant immunodeficiency (General variant gamma immunoglobulin hypothyroidism), dilated cardiomyopathy, fibrous lung disease, cryptogenic fibrosing alveolitis, post-inflammatory interstitial lung disease, interstitial pneumonia, connective tissue disease related Interstitial lung disease, mixed connective tissue disease-associated lung disease, systemic sclerosis-associated interstitial lung disease, rheumatoid arthritis-associated interstitial lung disease, systemic lupus erythematosus-associated lung disease, skin Myositis / polymyositis-associated lung disease, Hugh Glen's disease-associated lung disease, joint adhesion spondylitis-associated lung disease, vascular diffuse lung disease, heme-associated lung disease, medicine Induces interstitial lung disease, radiation fibrosis, occlusive bronchiolitis, chronic eosinophilic leukocyte pneumonia, lymphocytic invasive lung disease, post-infection interstitial lung disease Gouty arthritis, autoimmune hepatitis, type 1 autoimmune hepatitis (classic autoimmune or lupus-like hepatitis), type 2 autoimmune hepatitis (anti-LKM antibody hepatitis), autoimmune-mediated hypoglycemia, Type B insulin resistance with acanthosis nigricans, parathyroid hypothyroidism, acute immune disease associated with organ transplantation, chronic immune disease associated with organ transplantation, non-inflammatory osteoarthropathy, primary sclerosing bile duct Inflammation, idiopathic leukopenia, autoimmune neutropenia, nephropathy NOS, glomerulonephritis, micropolyangiitis of the kidney, discoid lupus erythematosus, idiopathic or NOS male infertility Disease, semen autoimmune disease, multiple sclerosis (all subtypes), insulin-dependent diabetes mellitus, sympathetic ophthalmia, pulmonary hypertension secondary to connective tissue disease, Gubold's syndrome, nodular polyarteritis Pulmonary manifestations, acute rheumatoid fever, rheumatoid spondylitis, Still's disease, systemic sclerosis, Takayasu's disease / arteritis, autoimmune thrombocytopenia, idiopathic thrombocytopenia, autoimmunity Thyroid disease, thyroid high energy disease, goiter autoimmune thyroid hypo energy disease (Hashimoto's disease), atrophic autoimmune thyroid hypo energy disease, primary myxedema, lens-derived uveitis, primary pulse Ductitis, white spot disease, allergic rhinitis (hay fever allergy), severe allergy, pet allergy, milk allergy, drug allergy, allergic rhinoconjunctivitis, eosinophilic esophagitis, eosinophilia, eosinophilia Gastroenteritis, cutaneous lupus erythematosus, eosinophilic esophagitis, eosinophilic syndrome, eosinophilic gastroenteritis, and diarrhea.

在本文提供的方法及組成物之一些實施例中，組成物進一步包含一或多種消炎劑。在本文提供的方法及組成物之一些實施例中，消炎劑為非類固醇消炎藥物(non-steroidal anti-inflammatory drug；NSAID)。示範性NSAID包括但不限於阿司匹靈、伊布洛芬、萘普生、塞來考昔、羅非昔布、待克菲那、二氟尼柳、依託度酸、非諾洛芬、氟比洛芬、酮洛芬、酮咯酸、甲芬那酸、美洛昔康、萘丁美酮、奧沙普秦、吡羅昔康、舒林酸、妥美汀及其組合。在一些實施例中，NSAID為免疫選擇性消炎衍生物(immune selective anti-inflammatory derivative；ImSAID)。 疾病之治療In some embodiments of the methods and compositions provided herein, the composition further comprises one or more anti-inflammatory agents. In some embodiments of the methods and compositions provided herein, the anti-inflammatory agent is a non-steroidal anti-inflammatory drug (NSAID). Exemplary NSAIDs include, but are not limited to, aspirin, ibuprofen, naproxen, celecoxib, rofecoxib, teflunafil, diflunisal, etodolac, fenoxyprofen, Flurbiprofen, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, oxaprozin, piroxicam, sulindac, tometin, and combinations thereof. In some embodiments, the NSAID is an immune selective anti-inflammatory derivative (ImSAID). Treatment of disease

在一個態樣中，本揭示內容提供用於受試者之疾病的治療之組成物及方法。在一個態樣中，且無限制的情況下，本文揭示的組成物可治療疾病，因為其投與導致CD8+ T細胞之增殖及/或累積之誘導。在一些實施例中，本揭示內容提供針對可藉由誘導CD8+ T細胞之增殖及/或累積來治療的疾病而用於受試者之疾病之治療的組成物及方法。在一些實施例中，可藉由誘導CD8+ T細胞之增殖及/或累積來治療的疾病為癌症、傳染性疾病、自體免疫疾病或過敏性疾病。In one aspect, the present disclosure provides compositions and methods for the treatment of a disease in a subject. In one aspect, and without limitation, the compositions disclosed herein can treat disease because its administration results in induction of the proliferation and / or accumulation of CD8 + T cells. In some embodiments, the present disclosure provides compositions and methods for the treatment of diseases in a subject for diseases that can be treated by inducing the proliferation and / or accumulation of CD8 + T cells. In some embodiments, the disease that can be treated by inducing the proliferation and / or accumulation of CD8 + T cells is cancer, infectious disease, autoimmune disease, or allergic disease.

在一個態樣中，本揭示內容提供治療受試者之疾病的方法，其包含以治療該疾病之有效量投與本文提供的任何組成物至該受試者。在本文提供的方法之一些實施例中，將組成物投與至受試者導致在該受試者之腸內CD8+ T細胞之增殖及/或累積之誘導。在本文提供的方法之一些實施例中，該受試者之腸內CD8+ T細胞之增殖及/或累積在相較於在該組成物之投與之前在該受試者之腸內CD8+ T細胞之增殖及/或累積時增加至少10%、至少20%、至少30%、至少40%、至少50%、至少100%或至少200%。在本文提供的方法之一些實施例中，將組成物投與至受試者導致在相較於在該組成物之投與之前該受試者之腸內的IFN-γ產生時該受試者之腸內IFN-γ產生之增加。在本文提供的方法之一些實施例中，將組成物投與至受試者導致在相較於在該組成物之投與之前在該受試者之腸內的IFN-γ產生時在該受試者之腸內IFN-γ產生之增加達至少10%、至少20%、至少30%、至少40%、至少50%、至少100%或至少200%。In one aspect, the disclosure provides a method of treating a disease in a subject, comprising administering to the subject any composition provided herein in an amount effective to treat the disease. In some embodiments of the methods provided herein, administering the composition to a subject results in induction of the proliferation and / or accumulation of CD8 + T cells in the intestine of the subject. In some embodiments of the methods provided herein, CD8 + T cells proliferate and / or accumulate in the intestine of the subject compared to CD8 + T cells in the intestine of the subject prior to administration of the composition The proliferation and / or accumulation is increased by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 100%, or at least 200%. In some embodiments of the methods provided herein, administering the composition to a subject results in the subject being IFN-γ produced in the intestine of the subject compared to prior to administration of the composition. Increased intestinal IFN-γ production. In some embodiments of the methods provided herein, administering the composition to a subject results in the subject receiving IFN-γ in the subject's intestine as compared to prior to administration of the composition. The increase in the intestinal IFN-γ production of the subject was at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 100%, or at least 200%.

本文描述的任何組成物可以治療或預防疾病(例如，癌症或傳染性疾病)之治療有效量或治療有效量之劑量投與至受試者。術語「治療(treat)」或「治療(treatment)」係指減少或減輕與疾病(例如，癌症或傳染性疾病)相關聯的症狀中之一或多者。術語「預防(prevent)」或「預防(prevention)」涵蓋預防性投與且減少疾病(例如，癌症或傳染性疾病)之發生率或該疾病之發生可能性。例如，在一些實施例中，本文提供的組成物之投與產生健康的微生物群，其誘導CD8+ T細胞之增殖及/或累積，進而保護受試者抵抗癌症及/或傳染性疾病。Any of the compositions described herein can be administered to a subject in a therapeutically effective amount or in a therapeutically effective amount of a disease (eg, cancer or infectious disease). The term "treat" or "treatment" refers to reducing or alleviating one or more of the symptoms associated with a disease (eg, cancer or infectious disease). The term "prevent" or "prevention" encompasses prophylactic administration and reduces the incidence or likelihood of a disease (eg, cancer or infectious disease). For example, in some embodiments, administration of the compositions provided herein produces a healthy microbiota that induces the proliferation and / or accumulation of CD8 + T cells, thereby protecting the subject against cancer and / or infectious diseases.

如本文所使用，諸如醫藥組成物之組成物之「治療有效量」為在受試者體內產生所要反應或結果的任何量，該所要反應或結果諸如本文描述的彼等者，包括但不限於感染之預防、癌症治療之免疫反應或增強的免疫反應及/或加強。應瞭解，術語有效量可以待投與的細菌或CFU之數量來表示。應進一步瞭解，一旦投與，細菌可倍增。因此，投與甚至相對小量之細菌可具有治療效應。As used herein, a "therapeutically effective amount" of a composition such as a pharmaceutical composition is any amount that produces a desired response or result in a subject, such as those described herein, including but not limited to Prevention of infection, immune response or enhanced immune response and / or strengthening of cancer treatment. It should be understood that the term effective amount may be expressed in terms of the number of bacteria or CFU to be administered. It should be further understood that once administered, bacteria can multiply. Therefore, administration of even relatively small amounts of bacteria can have a therapeutic effect.

在一些實施例中，本文描述的任何組成物之治療有效量為足以治療疾病，例如，增強受試者之存活，抑制感染及/或治療癌症的量。In some embodiments, a therapeutically effective amount of any of the compositions described herein is an amount sufficient to treat a disease, for example, enhance the survival of a subject, inhibit infection, and / or treat cancer.

本文描述的任何方法可用於治療受試者之癌症。如本文所使用的，治療癌症之方法涉及緩解或減輕與癌症相關聯的至少一種症狀，或減慢或逆轉癌症進程。治療癌症之方法可例如消除或減少受試者之腫瘤負擔，減少癌細胞之數量或複製，及/或預防、延遲或抑制轉移。Any of the methods described herein can be used to treat cancer in a subject. As used herein, a method of treating cancer involves alleviating or alleviating at least one symptom associated with cancer, or slowing or reversing the cancer process. Methods of treating cancer can, for example, eliminate or reduce the tumor burden on a subject, reduce the number or replication of cancer cells, and / or prevent, delay or inhibit metastasis.

本文亦提供用於治療或預防受試者之傳染性疾病的方法。如本文所使用的，治療傳染性疾病之方法可涉及緩解或減輕與感染相關聯的至少一種症狀，或減慢或逆轉感染進程。治療傳染性疾病之方法可例如消除或減少傳染性生物體(例如，細菌、病毒、真菌或寄生蟲)之負荷，或抑制或減少感染之一或多種症狀。亦如本文所使用的，術語「預防(prevent)」、「預防(prevention)」及「預防(preventing)」包括投與組成物至受試者以減少或延遲感染之臨床或亞臨床症狀、併發症、病理學或生物化學標記之表現的發作，或減少或抑制傳染性生物體(例如，細菌、病毒、真菌或寄生蟲)之傳播/傳輸。Also provided herein are methods for treating or preventing infectious diseases in a subject. As used herein, a method of treating an infectious disease may involve alleviating or alleviating at least one symptom associated with the infection, or slowing or reversing the course of the infection. Methods of treating infectious diseases may, for example, eliminate or reduce the load on infectious organisms (e.g., bacteria, viruses, fungi, or parasites), or inhibit or reduce one or more symptoms of infection. As also used herein, the terms "prevent", "prevention" and "preventing" include the administration of a composition to a subject to reduce or delay clinical or subclinical symptoms of infection, concomitant Of onset of symptoms, pathological or biochemical markers, or reduce or inhibit the transmission / transmission of infectious organisms (eg, bacteria, viruses, fungi or parasites).

本揭示內容之態樣係關於藉由投與治療有效量之本文描述的任何組成物來治療受試者之疾病或病狀的方法。在一些實施例中，受試者為哺乳類受試者，諸如人類、非人類靈長類動物、齧齒動物、兔、羊、豬、犬、貓、馬或母牛。在一些實施例中，受試者為人類受試者。Aspects of the disclosure are related to a method of treating a disease or condition in a subject by administering a therapeutically effective amount of any of the compositions described herein. In some embodiments, the subject is a mammalian subject, such as a human, non-human primate, rodent, rabbit, sheep, pig, dog, cat, horse, or cow. In some embodiments, the subject is a human subject.

本文描述的組成物及方法可結合諸如另外的治療劑之其他類型的療法一起使用(亦即，組合治療)。另外的組合療法之實例包括而不限於外科術、放射、基因療法及另外的治療劑之投與，該等治療劑諸如化療劑、抗生素、抗病毒劑、抗真菌劑、抗寄生蟲劑、免疫調節劑、消炎劑。一般而言，組合療法可與本文描述的組成物及方法同時地或順序地(以任何次序)投與。在一些實施例中，本文描述的任何組成物係與一或多種另外的治療劑同時投與，例如，以單劑量或以在實質上同時投與的多劑量來投與。The compositions and methods described herein can be used in conjunction with other types of therapy, such as additional therapeutic agents (ie, combination therapies). Examples of additional combination therapies include, without limitation, the administration of surgery, radiation, gene therapy, and additional therapeutic agents such as chemotherapeutics, antibiotics, antivirals, antifungals, antiparasites, immune Regulators, anti-inflammatory agents. In general, combination therapies can be administered simultaneously or sequentially (in any order) with the compositions and methods described herein. In some embodiments, any composition described herein is administered concurrently with one or more additional therapeutic agents, for example, in a single dose or in multiple doses administered substantially simultaneously.

在一些實施例中，本文描述的組成物係與一或多種另外的治療劑相伴地投與至受試者。在一些實施例中，本文描述的組成物係投與至受試者繼之以投與一或多種另外的治療劑。在一些實施例中，本文描述的任何組成物係投與至少約1天、2天、3天、4天、5天、6天、1週、2週、3週、4週、5週、6週、7週、8週、9週、10週、11週、12週、3個月、4個月、5個月、6個月或更多，之後投與一或多種另外的治療劑。替代地，在一些實施例中，一或多種治療劑係投與至受試者繼之以投與本文描述的任何組成物。在一些實施例中，一或多種治療劑係投與至少約1天、2天、3天、4天、5天、6天、1週、2週、3週、4週、5週、6週、7週、8週、9週、10週、11週、12週、3個月、4個月、5個月、6個月或更多，之後投與本文描述的任何組成物。 另外的方法In some embodiments, a composition described herein is administered to a subject in conjunction with one or more additional therapeutic agents. In some embodiments, a composition described herein is administered to a subject followed by administration of one or more additional therapeutic agents. In some embodiments, any composition described herein is administered for at least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 3 months, 4 months, 5 months, 6 months or more, after which one or more additional therapeutic agents are administered . Alternatively, in some embodiments, one or more therapeutic agents are administered to a subject followed by administration of any of the compositions described herein. In some embodiments, the one or more therapeutic agents are administered for at least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 Week, 7 week, 8 week, 9 week, 10 week, 11 week, 12 week, 3 month, 4 month, 5 month, 6 month or more, and then administer any composition described herein. Another method

亦在本揭示內容之範疇內的為評定本文描述的任何組成物之一或多種細菌菌株是否存在於受試者之腸內的方法。在一些實施例中，若在受試者之腸內偵測到少於細菌菌株之閾值數量，則本文描述的任何組成物係投與至受試者以增加受試者之腸內的細菌菌株之數量。在一些實施例中，方法進一步包含基於腸內偵測的細菌菌株之數量識別作為用於治療疾病之侯選者的受試者。Also within the scope of this disclosure is a method of assessing whether one or more bacterial strains of any of the compositions described herein are present in the intestine of a subject. In some embodiments, if less than a threshold number of bacterial strains is detected in the subject's intestine, any composition described herein is administered to the subject to increase the bacterial strain in the subject's intestine Of quantity. In some embodiments, the method further comprises identifying a subject as a candidate for treating a disease based on the number of bacterial strains detected in the intestine.

量測生物標誌物集合之位準亦可適用於評估及治療疾病。Measuring levels of biomarker sets can also be applied to assess and treat diseases.

一般而言，腸之細菌群體(例如，存在或不存在一或多種細菌菌株)可藉由評定自受試者獲得的諸如糞便樣本之樣本來判定。Generally, the bacterial population of the intestine (eg, the presence or absence of one or more bacterial strains) can be determined by assessing a sample, such as a stool sample, obtained from a subject.

在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內CD8+ T細胞之增殖及/或累積之誘導。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在受試者之腸內的IFN-γ產生之增加。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內所投與組成物之一或多種細菌菌株之存在。在本文提供的組成物之一些實施例中，所投與組成物之一或多種細菌菌株先前不存在於該受試者之腸內。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內所投與組成物之一或多種細菌菌株之植入。在本文提供的組成物之一些實施例中，所投與組成物之一或多種細菌菌株先前未植入該受試者之腸內。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內所投與組成物之細菌菌株數量之增加。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致該受試者之腸內所投與組成物之細菌菌株的植入數量之增加。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內的所投與組成物之細菌菌株之總細菌的豐度之增加。在本文提供的組成物之一些實施例中，將組成物投與至受試者導致在該受試者之腸內的所投與組成物之細菌菌株的植入總細菌菌株之增加。In some embodiments of the compositions provided herein, administering the composition to a subject results in induction of proliferation and / or accumulation of CD8 + T cells in the intestine of the subject. In some embodiments of the compositions provided herein, administering the composition to a subject results in an increase in IFN-γ production in the subject's intestine. In some embodiments of the compositions provided herein, administering the composition to a subject results in the presence of one or more bacterial strains of the composition administered in the intestine of the subject. In some embodiments of the compositions provided herein, one or more bacterial strains of the administered composition were not previously present in the intestine of the subject. In some embodiments of the compositions provided herein, administering the composition to a subject results in implantation of one or more bacterial strains of the composition administered in the intestine of the subject. In some embodiments of the compositions provided herein, one or more bacterial strains of the administered composition have not been previously implanted in the intestine of the subject. In some embodiments of the compositions provided herein, administering the composition to a subject results in an increase in the number of bacterial strains of the composition administered in the subject's intestine. In some embodiments of the compositions provided herein, administering the composition to a subject results in an increase in the number of implanted bacterial strains of the composition administered in the intestine of the subject. In some embodiments of the compositions provided herein, administering the composition to a subject results in an increase in the total bacterial abundance of the bacterial strain of the composition administered in the subject's intestine. In some embodiments of the compositions provided herein, administering the composition to a subject results in an increase in the total bacterial strain implanted in the subject's intestine of the bacterial strain of the administered composition.

在一個態樣中，本揭示內容提供一種方法，該方法包括判定本文提供的任何組成物之一或多種細菌物種是否存在於受試者之腸內，其中若存在小於100%、小於90%、小於80%、小於70%、小於60%、小於50%、小於40%、小於30%、小於20%、小於10%之細菌物種，或不存在細菌物種，則將組成物投與至該受試者。In one aspect, the present disclosure provides a method comprising determining whether one or more bacterial species of any of the compositions provided herein are present in the intestine of a subject, where less than 100%, less than 90%, Less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10% of bacterial species, or the absence of bacterial species, the composition is administered to the subject Tester.

在本文提供的方法之一些實施例中，受試者經歷或將經歷癌症治療。In some embodiments of the methods provided herein, the subject undergoes or will undergo cancer treatment.

在一個態樣中，本揭示內容提供用於判定是否預期受試者對癌症治療積極反應的方法，其中該方法包括判定本文提供的任何組成物之一或多種細菌是否存在於受試者之腸內，其中若存在小於100%、小於90%、小於80%、小於70%、小於60%、小於50%、小於40%、小於30%、小於20%、小於10%之細菌物種，或不存在細菌物種，則不預期該受試者對癌症治療積極反應。In one aspect, the present disclosure provides a method for determining whether a subject is expected to respond positively to cancer treatment, wherein the method includes determining whether one or more bacteria of any of the compositions provided herein are present in the subject's intestine Within, if there are less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, or not In the presence of bacterial species, the subject is not expected to respond positively to cancer treatment.

在本文提供的方法之一些實施例中，癌症治療為癌症免疫療法治療。In some embodiments of the methods provided herein, the cancer treatment is a cancer immunotherapy treatment.

在一個態樣中，本揭示內容提供用於降低受試者的病毒感染風險之方法，其中該方法包括判定本文提供的任何組成物之一或多種細菌物種是否存在於受試者之腸內，其中若存在小於100%、小於90%、小於80%、小於70%、小於60%、小於50%、小於40%、小於30%、小於20%、小於10%之細菌物種，或不存在細菌物種，則將組成物投與至該受試者，進而降低該受試者的病毒感染風險。In one aspect, the present disclosure provides a method for reducing the risk of viral infection in a subject, wherein the method includes determining whether one or more of the bacterial species provided herein are present in the intestine of the subject, Among them, if there are less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, or no bacteria Species, the composition is administered to the subject, thereby reducing the risk of viral infection in the subject.

在本文提供的方法之一些實施例中，判定細菌物種中之一或多者之存在係藉由將受試者之糞便物測序來進行。 醫藥組成物In some embodiments of the methods provided herein, determining the presence of one or more of the bacterial species is performed by sequencing the subject's fecal matter. Pharmaceutical composition

在一個態樣中，本揭示內容提供醫藥組成物，其包含本文提供的細菌菌株及細菌菌株之組合。在本文提供的組成物之一些實施例中，組成物為醫藥組成物。在本文提供的醫藥組成物之一些實施例中，醫藥組成物包含醫藥學上可接受的賦形劑。在本文提供的醫藥組成物之一些實施例中，醫藥組成物係配製用於口服投與。在本文提供的醫藥組成物之一些實施例中，醫藥組成物係配製用於直腸投與。在本文提供的醫藥組成物之一些實施例中，醫藥組成物係配製用於遞送至腸。在本文提供的醫藥組成物之一些實施例中，醫藥組成物係配製用於遞送至結腸。在本文提供的醫藥組成物之一些實施例中，細菌菌株中之一或多者係凍乾的。在本文提供的醫藥組成物之一些實施例中，醫藥組成物係呈膠囊形式。在本文提供的醫藥組成物之一些實施例中，醫藥組成物進一步包含pH敏感組成物，其包含一或多種腸聚合物。In one aspect, the disclosure provides a pharmaceutical composition comprising a bacterial strain and a combination of bacterial strains provided herein. In some embodiments of the composition provided herein, the composition is a pharmaceutical composition. In some embodiments of the pharmaceutical composition provided herein, the pharmaceutical composition comprises a pharmaceutically acceptable excipient. In some embodiments of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for oral administration. In some embodiments of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for rectal administration. In some embodiments of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for delivery to the intestine. In some embodiments of the pharmaceutical compositions provided herein, the pharmaceutical composition is formulated for delivery to the colon. In some embodiments of the pharmaceutical compositions provided herein, one or more of the bacterial strains are lyophilized. In some embodiments of the pharmaceutical composition provided herein, the pharmaceutical composition is in the form of a capsule. In some embodiments of the pharmaceutical composition provided herein, the pharmaceutical composition further comprises a pH sensitive composition comprising one or more enteric polymers.

本文描述的任何組成物(包括包含組成物之醫藥組成物及食物產品)可含有呈任何形式之細菌菌株，例如呈水性形式，諸如溶液或懸浮液，嵌入半固體形式，呈粉末形式或冷凍乾燥形式。在一些實施例中組成物或組成物之細菌菌株為凍乾的。在一些實施例中，組成物中細菌菌株之子集為凍乾的。將組成物、特定而言包含細菌之組成物凍乾之方法在此項技術中為熟知的。參見，例如，US 3,261,761；US 4,205,132；PCT公開案WO 2014/029578及WO 2012/098358，其以全文引用方式併入本文。細菌可作為組合凍乾及/或細菌可分開地凍乾且在投與之前組合。細菌菌株可在將其與其他細菌菌株組合之前與醫藥賦形劑組合，或多種凍乾細菌可在呈凍乾形式的同時組合，且一旦組合，細菌之混合物可隨後與醫藥賦形劑組合。在一些實施例中，細菌菌株為凍乾餅塊。在一些實施例中，包含一或多種細菌菌株之組成物為凍乾餅塊。Any composition described herein (including pharmaceutical compositions and food products comprising the composition) may contain bacterial strains in any form, such as in an aqueous form, such as a solution or suspension, embedded in a semi-solid form, in powder form, or freeze-dried form. In some embodiments the composition or bacterial strain of the composition is lyophilized. In some embodiments, a subset of the bacterial strains in the composition are lyophilized. Methods of lyophilizing a composition, particularly a composition comprising bacteria, are well known in the art. See, for example, US 3,261,761; US 4,205,132; PCT publications WO 2014/029578 and WO 2012/098358, which are incorporated herein by reference in their entirety. Bacteria can be lyophilized as a combination and / or bacteria can be lyophilized separately and combined before administration. The bacterial strain may be combined with a pharmaceutical excipient before combining it with other bacterial strains, or a plurality of lyophilized bacteria may be combined while being in a lyophilized form, and once combined, the mixture of bacteria may then be combined with a pharmaceutical excipient. In some embodiments, the bacterial strain is a lyophilized cake. In some embodiments, the composition comprising one or more bacterial strains is a lyophilized cake.

組成物之細菌菌株可使用在此項技術中熟知的發酵技術來製造。在一些實施例中，活性成分係使用厭氧發酵槽製造，該等厭氧發酵槽可支援厭氧細菌物種之快速生長。厭氧發酵槽可例如為攪拌槽式反應器或拋棄式wave式生物反應器。缺少動物組分的諸如BL培養基及EG培養基之培養基或該些培養基之類似型式可用於支援細菌物種之生長。細菌產物可藉由諸如離心及過濾之傳統技術自發酵培養液純化及濃縮，且可視情況藉由在此項技術中熟知的技術乾燥並凍乾。The bacterial strain of the composition can be produced using fermentation techniques well known in the art. In some embodiments, the active ingredients are manufactured using anaerobic fermentation tanks, which can support the rapid growth of anaerobic bacterial species. The anaerobic fermentation tank may be, for example, a stirred tank type reactor or a disposable wave type bioreactor. Media lacking animal components such as BL media and EG media or similar types of media can be used to support the growth of bacterial species. The bacterial product can be purified and concentrated from the fermentation broth by conventional techniques such as centrifugation and filtration, and optionally dried and lyophilized by techniques well known in the art.

在一些實施例中，細菌菌株之組成物可配製用於作為醫藥組成物投與。如本文所使用的術語「醫藥組成物」意味著由至少一種活性成分、諸如本文描述的任何兩種或更多種純化細菌菌株及可包括一或多種醫藥學上可接受的賦形劑之一或多種鈍性成分之混合或組合產生的產物。In some embodiments, the composition of the bacterial strain can be formulated for administration as a pharmaceutical composition. The term "pharmaceutical composition" as used herein means consisting of at least one active ingredient, such as any two or more purified bacterial strains described herein, and may include one of one or more pharmaceutically acceptable excipients A product produced by the mixing or combination of one or more inactive ingredients.

「可接受的」賦形劑係指必須與活性成分相容且對投與其的受試者無害的賦形劑。在一些實施例中，醫藥學上可接受的賦形劑係基於投與組成物之所欲路線，例如用於口服或鼻部投與之組成物可包含與用於直腸投與之組成物不同的醫藥學上可接受的賦形劑。賦形劑之實例包括無菌水、生理鹽水、溶劑、鹼性材料、乳化劑、懸浮劑、表面活性劑、穩定劑、調味劑、芳香劑、賦形劑、媒劑、防腐劑、黏合劑、稀釋劑、張力調整劑、安撫劑、增積劑、崩解劑、緩衝劑、包衣劑、潤滑劑、著色劑、甜味劑、增稠劑及增溶劑。"Acceptable" excipient means an excipient that must be compatible with the active ingredient and not harmful to the subject to whom it is administered. In some embodiments, the pharmaceutically acceptable excipient is based on the desired route of administration of the composition, for example, the composition for oral or nasal administration may comprise a composition different from the composition for rectal administration Pharmaceutically acceptable excipients. Examples of excipients include sterile water, physiological saline, solvents, alkaline materials, emulsifiers, suspending agents, surfactants, stabilizers, flavoring agents, fragrances, excipients, vehicles, preservatives, binders, Diluents, tonicity adjusters, soothing agents, builders, disintegrants, buffers, coatings, lubricants, colorants, sweeteners, thickeners and solubilizers.

醫藥組成物可根據熟知的方法製備且在此項技術中按慣例實踐(參見，例如，Remington ：The Science and Practice of Pharmacy，Mack Publishing Co.第20版2000)。本文描述的醫藥組成物可進一步包含呈凍乾配方或水溶液形式之任何載劑或穩定劑。可接受的賦形劑、載劑或穩定劑可包括例如緩衝液、抗氧化劑、防腐劑、聚合物、螯合試劑及/或表面活性劑。醫藥組成物較佳地在GMP條件下製造。醫藥組成物可例如以以下形式以經口、經鼻或腸胃外方式使用：膠囊、錠劑、丸劑、包囊、液體、粉末、顆粒、精細顆粒、薄膜包衣製劑、團塊、口含錠、舌下腺製劑、咀嚼劑、口頰製劑、糊狀物、糖漿、懸浮液、酏劑、乳液、擦劑、軟膏劑、硬膏劑、泥罨劑、經皮吸收系統、洗劑、吸入劑、氣霧劑、注射劑、栓劑及類似物。Pharmaceutical compositions can be prepared according to well-known methods and practiced routinely in the art (see, for example, Remington: The Science and Practice of Pharmacy, Mack Publishing Co. 20th edition 2000). The pharmaceutical composition described herein may further comprise any carrier or stabilizer in the form of a lyophilized formulation or an aqueous solution. Acceptable excipients, vehicles or stabilizers may include, for example, buffers, antioxidants, preservatives, polymers, chelating agents, and / or surfactants. The pharmaceutical composition is preferably manufactured under GMP conditions. The pharmaceutical composition can be used orally, nasally or parenterally, for example, in the form of capsules, tablets, pills, capsules, liquids, powders, granules, fine granules, film-coated preparations, lumps, orally lozenge , Sublingual gland preparation, chew, cheek preparation, paste, syrup, suspension, tincture, lotion, lotion, ointment, plaster, lozenge, transdermal absorption system, lotion, inhaler , Aerosols, injections, suppositories and the like.

在一些實施例中，細菌經配製用於遞送至腸(例如，小腸及/或結腸)。在一些實施例中，細菌係利用腸溶衣配製，從而增加細菌歷經胃中之惡劣環境之存活。腸溶衣為抵抗胃中之胃液作用以便併入其中之細菌將通過胃並進入腸中的腸溶衣。腸溶衣可在與腸液接觸時容易溶解，以便封裝在包衣中的細菌將釋放於腸道中。腸溶衣可由此項技術中熟知的聚合物及共聚物組成，諸如可商購的EUDRAGIT (Evonik Industries)。(參見，例如，Zhang，AAPS PharmSciTech，2016，17 (1)，56-67)。In some embodiments, the bacteria are formulated for delivery to the intestine (eg, the small intestine and / or colon). In some embodiments, the bacteria are formulated with an enteric coating to increase the survival of the bacteria through the harsh environment in the stomach. An enteric coating is an enteric coating that counteracts the effects of gastric juice in the stomach so that bacteria incorporated therein will pass through the stomach and enter the intestine. Enteric coatings can be easily dissolved when contacted with intestinal fluid, so that the bacteria encapsulated in the coating will be released into the intestinal tract. Enteric coatings can be composed of polymers and copolymers well known in the art, such as the commercially available EUDRAGIT (Evonik Industries). (See, for example, Zhang, AAPS PharmSciTech, 2016, 17 (1), 56-67).

細菌亦可經配製用於直腸遞送至腸(例如，結腸)。因此，在一些實施例中，細菌組成物可經配製用於藉由栓劑、結腸鏡檢查、內視鏡檢法、乙狀結腸鏡檢查或灌腸劑遞送。醫藥製劑或配方及尤其用於口服投與之醫藥製劑可包括另外的組分，其允許本揭示內容之組成物有效遞送至腸(例如，結腸)。可使用允許組成物遞送至腸(例如，結腸)的各種醫藥製劑。其實例包括pH敏感組成物，更特定而言，緩衝包囊配方或腸聚合物，其在腸聚合物通過胃之後pH變成鹼性時釋放其內容物。當用於配製醫藥製劑之pH敏感組成物時，pH敏感組成物較佳地為組成物之分解pH閾值在約6.8與約7.5之間的聚合物。此種數值範圍為其中在胃之遠側部分處pH朝向鹼性側變動，且因此為適用於遞送至結腸之適合範圍的範圍。應進一步瞭解，腸之每一部分(例如，十二指腸、空腸、回腸、盲腸、結腸及直腸)具有不同的生物化學及化學環境。例如，腸之部分具有不同的pH，從而允許藉由具有特定pH敏感性之組成物的靶向遞送。因此，本文提供的組成物可經配製用於藉由提供具有適當pH敏感性之配方來遞送至腸或腸之特定部分(例如，十二指腸、空腸、回腸、盲腸、結腸及直腸)。(參見，例如，Villena等人，Int J Pharm 20l5，487 (1-2)：314-9)。Bacteria can also be formulated for rectal delivery to the intestine (eg, the colon). Thus, in some embodiments, the bacterial composition can be formulated for delivery by suppository, colonoscopy, endoscopy, sigmoidoscopy, or enemas. Pharmaceutical formulations or formulations, and pharmaceutical formulations especially for oral administration, may include additional components that allow the compositions of the present disclosure to be effectively delivered to the intestine (eg, the colon). Various pharmaceutical formulations can be used that allow the composition to be delivered to the intestine (eg, the colon). Examples thereof include a pH-sensitive composition, and more specifically, a buffered encapsulation formulation or an intestinal polymer that releases its contents when the pH of the intestinal polymer passes through the stomach and becomes alkaline. When used to formulate a pH-sensitive composition for a pharmaceutical formulation, the pH-sensitive composition is preferably a polymer having a decomposition pH threshold between about 6.8 and about 7.5. Such a numerical range is a range in which the pH changes toward the alkaline side at the distal portion of the stomach, and is therefore a suitable range suitable for delivery to the colon. It should be further understood that each part of the intestine (eg, duodenum, jejunum, ileum, cecum, colon, and rectum) has a different biochemical and chemical environment. For example, parts of the intestine have different pHs, allowing targeted delivery by a composition with specific pH sensitivity. Accordingly, the compositions provided herein can be formulated for delivery to specific parts of the intestine or intestine (eg, duodenum, jejunum, ileum, cecum, colon, and rectum) by providing a formulation with appropriate pH sensitivity. (See, for example, Villena et al., Int J Pharm 2015, 487 (1-2): 314-9).

適用於遞送組成物至腸(例如，結腸)的醫藥製劑之另一實施例為確保藉由延遲內容物(例如，細菌菌株)之釋放達大致3至5小時來遞送至結腸的醫藥製劑，該3至5小時相應於小腸過渡時間。在用於延遲釋放的醫藥製劑之一個實施例中，水凝膠係用作殼體。水凝膠為水合的且在與胃腸液接觸時膨脹，結果使得內容物得以有效地釋放(主要在結腸中釋放)。延遲釋放劑量單位包括含有藥物之組成物，其具有包衣或選擇性地包衣待投與的藥物或活性成分之材料。此種選擇性包衣材料之實例包括活體內可降解聚合物、逐漸可水解聚合物、逐漸水溶性聚合物及/或酶可降解聚合物。用於有效地延遲釋放的多種包衣材料為可利用的且包括例如諸如羥基丙基纖維素之基於纖維素的聚合物、諸如甲基丙烯酸聚合物及共聚物的丙烯酸聚合物及共聚物，及諸如聚乙烯吡咯啶酮的乙烯基聚合物及共聚物。Another embodiment of a pharmaceutical formulation suitable for delivering a composition to the intestine (e.g., the colon) is to ensure that the pharmaceutical formulation is delivered to the colon by delaying the release of the content (e.g., a bacterial strain) for approximately 3 to 5 hours 3 to 5 hours correspond to the small bowel transition time. In one embodiment of a pharmaceutical formulation for delayed release, a hydrogel is used as the shell. The hydrogel is hydrated and swells when in contact with gastrointestinal fluid, with the result that the contents are effectively released (mainly in the colon). Delayed-release dosage units include pharmaceutical-containing compositions having materials that coat or selectively coat the drug or active ingredient to be administered. Examples of such selective coating materials include in vivo degradable polymers, gradually hydrolyzable polymers, gradually water-soluble polymers, and / or enzyme-degradable polymers. A variety of coating materials for effectively delaying release are available and include, for example, cellulose-based polymers such as hydroxypropyl cellulose, acrylic polymers and copolymers such as methacrylic polymers and copolymers, and Vinyl polymers and copolymers such as polyvinylpyrrolidone.

允許遞送至腸(例如，結腸)的醫藥組成物之另外實例包括生物黏附組成物，其特定地黏附至結腸黏膜(例如，在美國專利第6.368.586號之說明書中描述的聚合物)，及併入有蛋白酶抑制劑以用於尤其保護胃腸道中之生物醫藥製劑免於歸因於蛋白酶之活性而分解的組成物。Additional examples of pharmaceutical compositions that allow delivery to the intestine (e.g., colon) include bioadhesive compositions that specifically adhere to the colonic mucosa (e.g., polymers described in the specification of U.S. Patent No. 6.368.586), and Compositions incorporating protease inhibitors for protecting, in particular, biopharmaceutical preparations in the gastrointestinal tract from decomposition due to protease activity.

允許遞送至腸(例如，結腸)的系統之另一實例為藉由壓力變化遞送組成物至結腸之系統，以此方式，內容物係藉由利用在胃之遠側部分處細菌發酵中氣體之產生所引起的壓力變化來釋放。此種系統不受特別限制，且其更特定實例為膠囊，其具有分散在栓劑基質中之內容物且利用疏水性聚合物(例如，乙基纖維素)包衣。Another example of a system that allows delivery to the intestine (e.g., the colon) is a system that delivers a composition to the colon by a change in pressure. In this way, the contents are made by utilizing the gas in the fermentation of bacteria at the distal part of the stomach. The resulting pressure change is released. Such a system is not particularly limited, and a more specific example thereof is a capsule having a content dispersed in a suppository base and coated with a hydrophobic polymer (for example, ethyl cellulose).

允許遞送組成物至腸(例如，結腸)的系統之另一實例為包括包衣之組成物，該包衣可藉由存在於腸管(例如，結腸)中之酶移除，該酶諸如例如碳水化合物水解酶或碳水化合物還原酶。此種系統不受特定限制，且其更特定實例包括使用食物組分之系統，該等食物組分諸如非澱粉多醣、直鏈澱粉、黃原膠及偶氮聚合物。Another example of a system that allows delivery of the composition to the intestine (e.g., the colon) is a composition that includes a coating that can be removed by an enzyme present in the intestine (e.g., the colon), such as, for example, carbohydrate Compound hydrolase or carbohydrate reductase. Such systems are not particularly limited, and more specific examples thereof include systems using food components such as non-starch polysaccharides, amylose, xanthan gum, and azo polymers.

本文提供的組成物亦可藉由經由孔口之遞送(例如，鼻管)或經由外科術來遞送至特定標靶區域，諸如腸。另外，本文提供的經配製用於遞送至特定區域(例如，盲腸或結腸)之組成物可藉由管投與(例如，直接投與至小腸中)。將諸如管之機械遞送方法與諸如pH特定包衣之化學遞送方法組合允許遞送本文提供的組成物至所要標靶區域(例如，盲腸或結腸)。The compositions provided herein can also be delivered to a specific target area, such as the intestine, by delivery through the orifice (eg, a nasal canal) or via surgery. Additionally, compositions provided herein that are formulated for delivery to a specific area (e.g., the cecum or colon) can be administered via a tube (e.g., directly into the small intestine). Combining a mechanical delivery method such as a tube with a chemical delivery method such as a pH-specific coating allows delivery of a composition provided herein to a desired target area (eg, the cecum or colon).

包含細菌菌株之組成物係藉由熟習此項技術者所知的習知方法配製成醫藥學上可接受的劑型。給藥方案經調整以提供最佳的所要反應(例如，預防或治療效應)。在一些實施例中，組成物之劑型為錠劑、丸劑、膠囊、粉末、顆粒、溶液或栓劑。在一些實施例中，醫藥組成物係配製用於口服投與。在一些實施例中，醫藥組成物經配製以使得組成物或其部分之細菌在通過受試者之胃之後保持為有活力的。在一些實施例中，醫藥組成物經配製用於直腸投與，例如作為栓劑來投與。在一些實施例中，醫藥組成物經配製用於藉由提供適當的包衣(例如，pH特定包衣、可藉由標靶區域特定酶來降解的包衣或可結合存在於標靶區域中之受體的包衣)來遞送至腸或腸之特定區域(例如，結腸)。Compositions containing bacterial strains are formulated into pharmaceutically acceptable dosage forms by conventional methods known to those skilled in the art. The dosing regimen is adjusted to provide the best desired response (e.g., a prophylactic or therapeutic effect). In some embodiments, the dosage form of the composition is a tablet, pill, capsule, powder, granule, solution or suppository. In some embodiments, the pharmaceutical composition is formulated for oral administration. In some embodiments, the pharmaceutical composition is formulated such that the bacteria of the composition or a portion thereof remains viable after passing through the subject's stomach. In some embodiments, the pharmaceutical composition is formulated for rectal administration, for example, as a suppository. In some embodiments, the pharmaceutical composition is formulated for use by providing a suitable coating (e.g., a pH-specific coating, a coating that can be degraded by a target region-specific enzyme, or can be present in combination in the target region Coating of the receptor) to the intestine or a specific area of the intestine (e.g., the colon).

醫藥組成物中之活性成分之劑量可有所變化以便針對特定受試者、組成物及投與模式獲得有效達成所要醫藥反應而無毒性或對受試者不具有不利效應的活性成分之量。所選劑量位準取決於各種因素，包括所使用的特定組成物之活性、投與路線、投與時間、治療之持續時間、與所使用的特定組成物組合使用的其他藥物、化合物及/或材料、所治療的受試者之年齡、性別、重量、病狀、一般健康及先前醫療史，及類似因素。The dosage of the active ingredient in the pharmaceutical composition may be varied in order to obtain the amount of the active ingredient that is effective to achieve the desired medical response without toxicity or adverse effects on the subject for a particular subject, composition, and mode of administration. The dosage level chosen will depend on a variety of factors, including the activity of the particular composition used, the route of administration, the time of administration, the duration of treatment, other drugs, compounds and / or in combination with the particular composition used Materials, age, sex, weight, condition, general health and previous medical history of the subject being treated, and similar factors.

醫師、獸醫或其他訓練有素的行醫者可在低於達成所要治療效應所需的彼位準之位準下開始醫藥組成物之給藥且逐漸地增加劑量直至達成所要效應(例如，病原性感染之治療、病原性感染之細菌負擔之減少、毒素產生之減少或抑制)。一般而言，如本文描述的用於對人群之預防性治療的本文揭示的組成物之有效劑量取決於許多不同的因素變化，該等因素包括投與路線、受試者之生理狀態、受試者是人類還是動物、所投與的其他藥物及所要治療效應。需要滴定劑量來最佳化安全性及功效。在一些實施例中，給藥方案要求本文描述的任何組成物之劑量的口服投與。在一些實施例中，給藥方案要求本文描述的任何組成物之多個劑量的口服投與。在一些實施例中，組成物係經口投與受試者1次、2次、3次、4次、5次、6次、7次、8次、9次或至少10次。A physician, veterinarian, or other trained practitioner can begin the administration of a pharmaceutical composition below the level required to achieve the desired therapeutic effect and gradually increase the dose until the desired effect is achieved (e.g., pathogenicity Treatment of infections, reduction of bacterial burden of pathogenic infections, reduction or suppression of toxin production). In general, the effective dose of a composition disclosed herein for preventive treatment of a population as described herein will vary depending on a number of different factors including the route of administration, the physiological state of the subject, the test subject Whether the person is a human or an animal, other drugs administered, and the effect to be treated. Titration doses are required to optimize safety and efficacy. In some embodiments, the dosing regimen requires oral administration of a dose of any of the compositions described herein. In some embodiments, the dosing regimen requires oral administration of multiple doses of any of the compositions described herein. In some embodiments, the composition is administered to a subject orally once, twice, three times, four times, five times, six times, seven times, eight times, nine times, or at least ten times.

包括本文揭示的醫藥組成物之組成物包括具有一定範圍活性成分(例如，活細菌、呈孢子格式之細菌)之組成物。組成物中之細菌量可以重量、細菌數量及/或CFU (菌落形成單位)表示。在一些實施例中，本文揭示的醫藥組成物含有每劑量之量約10、約102 、約103 、約104 、約105 、約106 、約107 、約108 、約109 、約1010 、約1011 、約10l2 、約10l3 或更多的組成物之每一細菌。在一些實施例中，本文揭示的醫藥組成物含有每劑量之量約10、約102 、約103 、約104 、約105 、約106 、約107 、約108 、約109 、約1010 、約1011 、約1012 、約10l3 或更多的總細菌。應進一步瞭解，組成物之細菌可以不同量存在。因此，例如，作為非限制性實例，組成物可包括103 之細菌A、104 之細菌B及106 之細菌C。在一些實施例中，本文揭示的醫藥組成物含有每劑量之量約10、約102 、約103 、約104 、約105 、約106 、約107 、約108 、約109 、約1010 、約1011 、約10l2 、約10l3 或更多CFU的組成物中之每一細菌。在一些實施例中，本文揭示的醫藥組成物含有對每劑量之量組合的所有細菌而言總計約101 、約102 、約103 、約104 、約105 、約106 、約107 、約108 、約109 、約1010 、約1011 、約10l2 、約10l3 或更多的CFU。如上文論述的，組成物之細菌可以不同量存在。在一些實施例中，本文揭示的醫藥組成物含有每劑量之量約10-7 、約10-6 、約10-5 、約10-4 、約10-3 、約10-2 、約10-1 或更多公克的組成物中之每一細菌。在一些實施例中，本文揭示的醫藥組成物含有對每劑量之量組合的所有細菌而言總計約10-7 、約10-6 、約10-5 、約10-4 、約10-3 、約10-2 、約10-1 或更多公克。在一些實施例中，劑量之量為一個投與裝置量(例如，一個錠劑、丸劑或膠囊)。在一些實施例中，劑量之量為在特定時期(例如，一天或一週)投與的量。Compositions including the pharmaceutical compositions disclosed herein include compositions having a range of active ingredients (e.g., live bacteria, bacteria in a spore format). The amount of bacteria in the composition can be expressed by weight, number of bacteria, and / or CFU (colony forming units). In some embodiments, the pharmaceutical compositions disclosed herein contain about 10, about 10 2 , about 10 3 , about 10 4 , about 10 5 , about 10 6 , about 10 7 , about 10 8 , about 10 per dose. 9 , about 10 10 , about 10 11 , about 10 l2 , about 10 l3 or more of each bacterium of the composition. In some embodiments, the pharmaceutical compositions disclosed herein contain about 10, about 10 2 , about 10 3 , about 10 4 , about 10 5 , about 10 6 , about 10 7 , about 10 8 , about 10 per dose. 9 , about 10 10 , about 10 11 , about 10 12 , about 10 13 or more total bacteria. It should be further understood that the bacteria of the composition may be present in different amounts. Thus, for example, as a non-limiting example, the composition may include 10 3 bacteria B, 10 4 bacteria B, and 10 6 bacteria C. In some embodiments, the pharmaceutical compositions disclosed herein contain about 10, about 10 2 , about 10 3 , about 10 4 , about 10 5 , about 10 6 , about 10 7 , about 10 8 , about 10 per dose. 9, about 1010, about 1011, about 10 L2, or more composition of about 10 CFU of each of the bacteria in L3. In some embodiments, the pharmaceutical composition disclosed herein contains a total of about 10 1 , about 10 2 , about 10 3 , about 10 4 , about 10 5 , about 10 6 , about 10 10 7 , about 10 8 , about 10 9 , about 10 10 , about 10 11 , about 10 l2 , about 10 l3, or more CFU. As discussed above, the bacteria of the composition may be present in different amounts. In some embodiments, the pharmaceutical compositions disclosed herein contain about 10-7 per dose of about 10 -6, about 10-5 to about 10-4, about 10-3 to about 10-2, about 10 - 1 or more grams of each bacterium in the composition. In some embodiments, the pharmaceutical composition disclosed herein contains a total of about 10 -7 , about 10 -6 , about 10 -5 , about 10 -4 , about 10 -3 , for all bacteria in a combination of amounts per dose, About 10 -2 , about 10 -1 or more grams. In some embodiments, the amount of the dose is that of a single administration device (eg, a lozenge, pill, or capsule). In some embodiments, the amount of dose is the amount administered over a specific period (eg, a day or a week).

在一些實施例中，本文揭示的醫藥組成物含有每劑量之量10與10l3 之間、102 與10l3 之間、103 與10l3 之間、104 與10l3 之間、105 與10l3 之間、106 與10l3 之間、107 與10l3 之間、108 與10l3 之間、109 與10l3 之間、1010 與10l3 之間、1011 與10l3 之間、10l2 與10l3 之間、10與10l2 之間、102 與10l2 之間、103 與10l2 之間、104 與10l2 之間、105 與1012 之間、106 與1012 之間、107 與1012 之間、108 與1012 之間、109 與1012 之間、1010 與1012 之間、1011 與1012 之間、10與1011 之間、102 與1011 之間、103 與1013 之間、104 與1013 之間、105 與1013 之間、106 與1013 之間、107 與1011 之間、108 與1011 之間、109 與1011 之間、1010 與1011 之間、10與1010 之間、102 與1010 之間、103 與1010 之間、104 與1010 之間、105 與1010 之間、106 與1010 之間、107 與1010 之間、108 與1010 之間、109 與1010 之間、10與109 之間、102 與109 之間、103 與109 之間、104 與109 之間、105 與109 之間、106 與109 之間、107 與109 之間、108 與109 之間、10與108 之間、102 與108 之間、103 與108 之間、104 與108 之間、105 與108 之間、106 與108 之間、107 與108 之間、10與107 之間、102 與107 之間、103 與107 之間、104 與107 之間、105 與107 之間、106 與107 之間、10與106 之間、102 與106 之間、103 與106 之間、104 與106 之間、105 與106 之間、10與105 之間、102 與105 之間、103 與105 之間、104 與105 之間、10與104 之間、102 與104 之間、103 與104 之間、10與103 之間、102 與103 之間或10與102 之間的組成物之每一細菌。在一些實施例中，本文揭示的醫藥組成物含有每劑量之量10與1013 之間、102 與1013 之間、103 與1013 之間、104 與1013 之間、105 與1013 之間、106 與1013 之間、107 與1013 之間、108 與1013 之間、109 與1013 之間、1010 與1013 之間、1011 與1013 之間、1012 與1013 之間、10與1012 之間、102 與1012 之間、103 與1012 之間、104 與1012 之間、105 與1012 之間、106 與1012 之間、107 與1012 之間、108 與1012 之間、109 與1012 之間、1010 與1012 之間、1011 與1012 之間、10與1011 之間、102 與1011 之間、103 與1013 之間、104 與1013 之間、105 與1013 之間、106 與1013 之間、107 與1011 之間、108 與1011 之間、109 與1011 之間、1010 與1011 之間、10與1010 之間、102 與1010 之間、103 與1010 之間、104 與1010 之間、105 與1010 之間、106 與1010 之間、107 與1010 之間、108 與1010 之間、109 與1010 之間、10與109 之間、102 與109 之間、103 與109 之間、104 與109 之間、105 與109 之間、106 與109 之間、107 與109 之間、108 與109 之間、10與108 之間、102 與108 之間、103 與108 之間、104 與108 之間、105 與108 之間、106 與108 之間、107 與108 之間、10與107 之間、102 與107 之間、103 與107 之間、104 與107 之間、105 與107 之間、106 與107 之間、10與106 之間、102 與106 之間、103 與106 之間、104 與106 之間、105 與106 之間、10與105 之間、102 與105 之間、103 與105 之間、104 與105 之間、10與104 之間、102 與104 之間、103 與104 之間、10與103 之間、102 與103 之間或10與102 之間的總細菌。In some embodiments, the pharmaceutical composition disclosed herein contains an amount per dose between 10 and 10 l3, between 10 2 and 10 l3, between 10 3 and 10 l3, between 10 4 and 10 l3 , and 10 5 Between 10 l3 , 10 6 and 10 l3 , 10 7 and 10 l3 , 10 8 and 10 l3 , 10 9 and 10 l3 , 10 10 and 10 l3 , 10 11 and 10 Between l3 , 10 l2 and 10 l3, between 10 and 10 l2, between 10 2 and 10 l2, between 10 3 and 10 l2, between 10 4 and 10 l2, between 10 5 and 10 12 , Between 10 6 and 10 12, between 10 7 and 10 12, between 10 8 and 10 12, between 10 9 and 10 12, between 10 10 and 10 12, between 10 11 and 10 12 , 10 Between 10 11 and 10 2 and 10 11 between 10 3 and 10 13, between 10 4 and 10 13, between 10 5 and 10 13, between 10 6 and 10 13 , 10 7 and 10 Between 11 , 10 8 and 10 11, between 10 9 and 10 11 , 10 10 and 10 11 , 10 and 10 10 , 10 2 and 10 10 , 10 3 and 10 10 , 10 4 and 10 10 , 10 5 and 10 10 , 10 6 and 10 10 , 10 7 and 10 10 , 10 8 and 10 10 , 10 9 and 10 10 , 10 Between 10 9 and 10 2 and 10 9 and 10 3 and Between 10 9 and 10 4 and 10 9, between 10 5 and 10 9, between 10 6 and 10 9, between 10 7 and 10 9, between 10 8 and 10 9 and between 10 and 10 8 Between 10 2 and 10 8, between 10 3 and 10 8, between 10 4 and 10 8, between 10 5 and 10 8, between 10 6 and 10 8, between 10 7 and 10 8 , Between 10 and 10 7, between 10 2 and 10 7 between 10 3 and 10 7, between 10 4 and 10 7, between 10 5 and 10 7, between 10 6 and 10 7 , 10 and 10 Between 6 , 10 2 and 10 6, between 10 3 and 10 6, between 10 4 and 10 6, between 10 5 and 10 6, between 10 and 10 5, and between 10 2 and 10 5 , Between 10 3 and 10 5, between 10 4 and 10 5, between 10 and 10 4, between 10 2 and 10 4, between 10 3 and 10 4, between 10 and 10 3 , 10 2 and Each bacterium has a composition between 10 3 or 10 and 10 2 . In some embodiments, the pharmaceutical composition disclosed herein contains an amount per dose between 10 and 10 13, between 10 2 and 10 13, between 10 3 and 10 13, between 10 4 and 10 13 , and 10 5 between 13 and 10, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 10 and 10 10 13 10 11 10 Between 13 , 10 12 and 10 13, between 10 and 10 12, between 10 2 and 10 12, between 10 3 and 10 12, between 10 4 and 10 12, and between 10 5 and 10 12 , Between 10 6 and 10 12, between 10 7 and 10 12, between 10 8 and 10 12, between 10 9 and 10 12, between 10 10 and 10 12, between 10 11 and 10 12 , 10 Between 10 11 and 10 2 and 10 11 between 10 3 and 10 13, between 10 4 and 10 13, between 10 5 and 10 13, between 10 6 and 10 13 , 10 7 and 10 Between 11 , 10 8 and 10 11, between 10 9 and 10 11 , 10 10 and 10 11 , 10 and 10 10 , 10 2 and 10 10 , 10 3 and 10 10 , 10 4 and 10 10 , 10 5 and 10 10 , 10 6 and 10 10 , 10 7 and 10 10 , 10 8 and 10 10 , 10 9 and 10 10 , 10 Between 10 9 and 10 2 and 10 9 and 10 3 and Between 10 9 and 10 4 and 10 9, between 10 5 and 10 9, between 10 6 and 10 9, between 10 7 and 10 9, between 10 8 and 10 9 and between 10 and 10 8 Between 10 2 and 10 8, between 10 3 and 10 8, between 10 4 and 10 8, between 10 5 and 10 8, between 10 6 and 10 8, between 10 7 and 10 8 , Between 10 and 10 7, between 10 2 and 10 7 between 10 3 and 10 7, between 10 4 and 10 7, between 10 5 and 10 7, between 10 6 and 10 7 , 10 and 10 Between 6 , 10 2 and 10 6, between 10 3 and 10 6, between 10 4 and 10 6, between 10 5 and 10 6, between 10 and 10 5, and between 10 2 and 10 5 , Between 10 3 and 10 5, between 10 4 and 10 5, between 10 and 10 4, between 10 2 and 10 4, between 10 3 and 10 4, between 10 and 10 3 , 10 2 and Total bacteria between 10 3 or 10 and 10 2 .

在一些實施例中，本文揭示的醫藥組成物含有每劑量之量10與1013 之間、102 與1013 之間、103 與1013 之間、104 與1013 之間、105 與1013 之間、106 與1013 之間、107 與1013 之間、108 與1013 之間、109 與1013 之間、1010 與1013 之間、1011 與1013 之間、1012 與1013 之間、10與1012 之間、102 與1012 之間、103 與1012 之間、104 與1012 之間、105 與1012 之間、106 與1012 之間、107 與1012 之間、108 與1012 之間、109 與1012 之間、1010 與1012 之間、1011 與1012 之間、10與1011 之間、102 與1011 之間、103 與1013 之間、104 與1013 之間、105 與1013 之間、106 與1013 之間、107 與1011 之間、108 與1011 之間、109 與1011 之間、1010 與1011 之間、10與1010 之間、102 與1010 之間、103 與1010 之間、104 與1010 之間、105 與1010 之間、106 與1010 之間、107 與1010 之間、108 與1010 之間、109 與1010 之間、10與109 之間、102 與109 之間、103 與109 之間、104 與109 之間、105 與109 之間、106 與109 之間、107 與109 之間、108 與109 之間、10與108 之間、102 與108 之間、103 與108 之間、104 與108 之間、105 與108 之間、106 與108 之間、107 與108 之間、10與107 之間、102 與107 之間、103 與107 之間、104 與107 之間、105 與107 之間、106 與107 之間、10與106 之間、102 與106 之間、103 與106 之間、104 與106 之間、105 與106 之間、10與105 之間、102 與105 之間、103 與105 之間、104 與105 之間、10與104 之間、102 與104 之間、103 與104 之間、10與103 之間、102 與103 之間或10與102 之間的CFU的組成物中之每一細菌。在一些實施例中，本文揭示的醫藥組成物含有每劑量之量10與1013 之間、102 與1013 之間、103 與1013 之間、104 與1013 之間、105 與1013 之間、106 與1013 之間、107 與1013 之間、108 與1013 之間、109 與1013 之間、1010 與1013 之間、1011 與1013 之間、1012 與1013 之間、10與1012 之間、102 與1012 之間、103 與1012 之間、104 與1012 之間、105 與1012 之間、106 與1012 之間、107 與1012 之間、108 與1012 之間、109 與1012 之間、1010 與1012 之間、1011 與1012 之間、10與1011 之間、102 與1011 之間、103 與1013 之間、104 與1013 之間、105 與1013 之間、106 與10l3 之間、107 與1011 之間、108 與1011 之間、109 與1011 之間、1010 與1011 之間、10與1010 之間、102 與1010 之間、103 與1010 之間、104 與1010 之間、105 與1010 之間、106 與1010 之間、107 與1010 之間、108 與1010 之間、109 與1010 之間、10與109 之間、102 與109 之間、103 與109 之間、104 與109 之間、105 與109 之間、106 與109 之間、107 與109 之間、108 與109 之間、10與108 之間、102 與108 之間、103 與108 之間、104 與108 之間、105 與108 之間、106 與108 之間、107 與108 之間、10與107 之間、102 與107 之間、103 與107 之間、104 與107 之間、105 與107 之間、106 與107 之間、10與106 之間、102 與106 之間、103 與106 之間、104 與106 之間、105 與106 之間、10與105 之間、102 與105 之間、103 與105 之間、104 與105 之間、10與104 之間、102 與104 之間、103 與104 之間、10與103 之間、102 與103 之間或10與102 之間的總CFU。In some embodiments, the pharmaceutical composition disclosed herein contains an amount per dose between 10 and 10 13, between 10 2 and 10 13, between 10 3 and 10 13, between 10 4 and 10 13 , and 10 5 between 13 and 10, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 10 and 10 10 13 10 11 10 Between 13 , 10 12 and 10 13, between 10 and 10 12, between 10 2 and 10 12, between 10 3 and 10 12, between 10 4 and 10 12, and between 10 5 and 10 12 , Between 10 6 and 10 12, between 10 7 and 10 12, between 10 8 and 10 12, between 10 9 and 10 12, between 10 10 and 10 12, between 10 11 and 10 12 , 10 Between 10 11 and 10 2 and 10 11 between 10 3 and 10 13, between 10 4 and 10 13, between 10 5 and 10 13, between 10 6 and 10 13 , 10 7 and 10 Between 11 , 10 8 and 10 11, between 10 9 and 10 11 , 10 10 and 10 11 , 10 and 10 10 , 10 2 and 10 10 , 10 3 and 10 10 , 10 4 and 10 10 , 10 5 and 10 10 , 10 6 and 10 10 , 10 7 and 10 10 , 10 8 and 10 10 , 10 9 and 10 10 , 10 Between 10 9 and 10 2 and 10 9 and 10 3 and Between 10 9 and 10 4 and 10 9, between 10 5 and 10 9, between 10 6 and 10 9, between 10 7 and 10 9, between 10 8 and 10 9 and between 10 and 10 8 Between 10 2 and 10 8, between 10 3 and 10 8, between 10 4 and 10 8, between 10 5 and 10 8, between 10 6 and 10 8, between 10 7 and 10 8 , Between 10 and 10 7, between 10 2 and 10 7 between 10 3 and 10 7, between 10 4 and 10 7, between 10 5 and 10 7, between 10 6 and 10 7 , 10 and 10 Between 6 , 10 2 and 10 6, between 10 3 and 10 6, between 10 4 and 10 6, between 10 5 and 10 6, between 10 and 10 5, and between 10 2 and 10 5 , Between 10 3 and 10 5, between 10 4 and 10 5, between 10 and 10 4, between 10 2 and 10 4, between 10 3 and 10 4, between 10 and 10 3 , 10 2 and Each bacterium in the composition of CFU between 10 3 or 10 and 10 2 . In some embodiments, the pharmaceutical composition disclosed herein contains an amount per dose between 10 and 10 13, between 10 2 and 10 13, between 10 3 and 10 13, between 10 4 and 10 13 , and 10 5 between 13 and 10, between 106 and 1013, between 107 and 1013, between 108 and 1013, between 109 and 1013, between 10 and 10 10 13 10 11 10 Between 13 , 10 12 and 10 13, between 10 and 10 12, between 10 2 and 10 12, between 10 3 and 10 12, between 10 4 and 10 12, and between 10 5 and 10 12 , Between 10 6 and 10 12, between 10 7 and 10 12, between 10 8 and 10 12, between 10 9 and 10 12, between 10 10 and 10 12, between 10 11 and 10 12 , 10 Between 10 11 and 10 2 and 10 11 between 10 3 and 10 13, between 10 4 and 10 13, between 10 5 and 10 13, between 10 6 and 10 l3 , 10 7 and 10 Between 11 , 10 8 and 10 11, between 10 9 and 10 11 , 10 10 and 10 11 , 10 and 10 10 , 10 2 and 10 10 , 10 3 and 10 10 , 10 4 and 10 10 , 10 5 and 10 10 , 10 6 and 10 10 , 10 7 and 10 10 , 10 8 and 10 10 , 10 9 and 10 10 , 10 Between 10 9 and 10 2 and 10 9 and 10 3 and Between 10 9 and 10 4 and 10 9, between 10 5 and 10 9, between 10 6 and 10 9, between 10 7 and 10 9, between 10 8 and 10 9 and between 10 and 10 8 Between 10 2 and 10 8, between 10 3 and 10 8, between 10 4 and 10 8, between 10 5 and 10 8, between 10 6 and 10 8, between 10 7 and 10 8 , Between 10 and 10 7, between 10 2 and 10 7 between 10 3 and 10 7, between 10 4 and 10 7, between 10 5 and 10 7, between 10 6 and 10 7 , 10 and 10 Between 6 , 10 2 and 10 6, between 10 3 and 10 6, between 10 4 and 10 6, between 10 5 and 10 6, between 10 and 10 5, and between 10 2 and 10 5 , Between 10 3 and 10 5, between 10 4 and 10 5, between 10 and 10 4, between 10 2 and 10 4, between 10 3 and 10 4, between 10 and 10 3 , 10 2 and Total CFU between 10 3 or 10 and 10 2 .

在一些實施例中，本文揭示的醫藥組成物含有每劑量之量10-7 與10-1 之間、10-6 與10-1 之間、10-5 與10-1 之間、10-4 與10-1 之間、10-3 與10-1 之間、10-2 與10-1 之間、10-7 與10-2 之間、10-6 與10-2 之間、10-5 與10-2 之間、10-4 與10-2 之間、10-3 與10-2 之間、10-7 與10-3 之間、10-6 與10-3 之間、10-5 與10-3 之間、10-4 與10-3 之間、10-7 與10-4 之間、10-6 與10-4 之間、10-5 與10-4 之間、10-7 與10-5 之間、10-6 與10-5 之間或10-7 與10-6 之間的公克的組成物中之每一細菌。在一些實施例中，本文揭示的醫藥組成物含有每劑量之量10-7 與10-1 之間、10-6 與10-1 之間、10-5 與10-1 之間、10-4 與10-1 之間、10-3 與10-1 之間、10-2 與10-1 之間、10-7 與10-2 之間、10-6 與10-2 之間、10-5 與10-2 之間、10-4 與10-2 之間、10-3 與10-2 之間、10-7 與10-3 之間、10-6 與10-3 之間、10-5 與10-3 之間、10-4 與10-3 之間、10-7 與10-4 之間、10-6 與10-4 之間、10-5 與10-4 之間、10-7 與10-5 之間、10-6 與10-5 之間或10-7 與10-6 之間的公克的組合的所有細菌。In some embodiments, the pharmaceutical compositions disclosed herein contain an amount per dose between 10 -7 and 10 -1, between 10 -6 and 10 -1, between 10 -5 and 10 -1 , and 10 -4 Between 10 -1 , 10 -3 and 10 -1, between 10 -2 and 10 -1, between 10 -7 and 10 -2, between 10 -6 and 10 -2 , 10 -5 Between 10 -2 , 10 -4 and 10 -2, between 10 -3 and 10 -2, between 10 -7 and 10 -3, between 10 -6 and 10 -3 , 10 -5 Between 10 -3 , 10 -4 and 10 -3, between 10 -7 and 10 -4, between 10 -6 and 10 -4, between 10 -5 and 10 -4 , and 10 -7 Each gram of the composition is between 10 and 5 , 10-6 and 10-5 , or 10-7 and 10-6 . In some embodiments, the pharmaceutical compositions disclosed herein contain an amount per dose between 10 -7 and 10 -1, between 10 -6 and 10 -1, between 10 -5 and 10 -1 , and 10 -4 Between 10 -1 , 10 -3 and 10 -1, between 10 -2 and 10 -1, between 10 -7 and 10 -2, between 10 -6 and 10 -2 , 10 -5 Between 10 -2 , 10 -4 and 10 -2, between 10 -3 and 10 -2, between 10 -7 and 10 -3, between 10 -6 and 10 -3 , 10 -5 Between 10 -3 , 10 -4 and 10 -3, between 10 -7 and 10 -4, between 10 -6 and 10 -4, between 10 -5 and 10 -4 , and 10 -7 All bacteria with a combination of 10 -5 , 10 -6 and 10 -5 or between 10 -7 and 10 -6 .

在一個態樣中，本揭示內容提供包含本文提供的任何組成物及養分的食物產品。亦在本揭示內容之範疇內的為包含本文描述的任何細菌菌株及養分之食物產品。一般而言，食物產品意欲供人類或動物消耗。本文描述的任何細菌菌株可配製為食物產品。在一些實施例中，細菌菌株係配製為呈孢子形式之食物產品。在一些實施例中，細菌菌株係配製為呈營養形式之食物產品。在一些實施例中，食物產品包含營養細菌及呈孢子形式之細菌兩者。本文揭示的組成物可用於食物或飲料，諸如健康食品或飲料、用於嬰兒之食物或飲料、用於孕婦、運動員、老人或其他指定群組之食物或飲料、功能性食品、飲料、用於指定健康用途的食物或飲料、膳食補充劑、用於患者之食物或飲料，或動物飼料。食物及飲料之非限制性實例包括各種飲料，諸如果汁，提神飲料、茶葉飲料、飲用製劑、果凍飲料及功能性飲料；酒精飲料，諸如啤酒；含有碳水化合物之食物，諸如水稻食物產品、麵條、麵包及麵食；糊狀產品，諸如魚肉火腿、香腸、海鮮之糊狀產品；殺菌袋裝產品，諸如咖哩飯、以稠澱粉醬料、湯敷飾的食物；乳製品，諸如牛奶、奶飲料、冰淇淋、乾酪及酸酪乳；發酵產品，諸如發酵豆醬、酸酪乳、發酵飲料及醃菜；豆製品；各種糖果甜點產品，諸如西方糖果甜點產品，包括餅乾、小甜餅及類似物，日文糖果甜點產品，包括蒸豆沙包、軟紅豆果凍及類似物、糖果、口香糖、膠狀製品、冷甜點，包括果凍、奶油焦糖及冷凍甜點；速食食品，諸如速食湯及速食大豆湯；可微波處理食物；及類似物。另外，實例亦包括以粉末、顆粒、錠劑、膠囊、液體、糊狀物及果凍形式製備的健康食品及飲料。In one aspect, the disclosure provides a food product comprising any of the compositions and nutrients provided herein. Also within the scope of this disclosure are food products comprising any of the bacterial strains and nutrients described herein. In general, food products are intended for human or animal consumption. Any bacterial strain described herein can be formulated as a food product. In some embodiments, the bacterial strain is formulated as a food product in the form of spores. In some embodiments, the bacterial strain is formulated as a food product in a nutritional form. In some embodiments, the food product includes both vegetative bacteria and bacteria in the form of spores. The compositions disclosed herein can be used in foods or beverages, such as health foods or beverages, foods or beverages for infants, foods or beverages for pregnant women, athletes, the elderly or other designated groups, functional foods, beverages, Food or drink for specified health uses, dietary supplements, food or drink for patients, or animal feed. Non-limiting examples of food and beverages include various beverages such as fruit juices, refreshing beverages, tea beverages, drinking preparations, jelly beverages and functional beverages; alcoholic beverages such as beer; foods containing carbohydrates such as rice food products, noodles, Bread and pasta; pasty products such as fish, ham, sausage, seafood paste products; sterilized bag products such as curry rice, foods decorated with thick starch sauces, soups; dairy products such as milk, milk drinks, Ice cream, cheese and yogurt, fermented products such as fermented soy sauce, yogurt, fermented drinks and pickles; soy products; various confectionery products, such as western confectionery products, including biscuits, cookies, and the like, Japanese confectionery products, including steamed bean paste bags, soft red bean jelly and the like, confectionery, chewing gum, jelly products, cold desserts, including jelly, butter caramel, and frozen desserts; fast foods such as instant soups and instant soybeans Soup; microwaveable food; and the like. In addition, examples include health foods and beverages prepared in the form of powders, granules, tablets, capsules, liquids, pastes, and jellies.

含有本文描述的細菌菌株之食物產品可使用此項技術中已知的方法產生且可含有與本文提供的醫藥組成物相同量之細菌(例如，以重量計之量或CFU)。選擇食物產品中之細菌之適當量可取決於各種因素，包括例如，食物產品之服務規模、食物產品之消耗頻率、食物產品中含有的特定細菌菌株、食物產品中之水量及/或用於食物產品中之細菌之存活的另外條件。Food products containing the bacterial strains described herein may be produced using methods known in the art and may contain the same amount of bacteria (eg, by weight or CFU) as the pharmaceutical composition provided herein. Choosing the appropriate amount of bacteria in a food product may depend on various factors, including, for example, the scale of service of the food product, the frequency of consumption of the food product, the specific bacterial strains contained in the food product, the amount of water in the food product, and / or its use in food Additional conditions for the survival of bacteria in the product.

可配製來含有本文描述的任何細菌菌株之食物產品之實例包括而不限於飲料、飲用物、條、小吃、乳製品、糖果甜點產品、穀物產品、即食食品、諸如營養補充配方之營養配方、食物或飲料添加劑。Examples of food products that can be formulated to contain any of the bacterial strains described herein include, without limitation, beverages, potables, bars, snacks, dairy products, confectionery products, cereal products, ready-to-eat foods, nutritional formulas such as nutritional supplement formulas, foods Or beverage additives.

在一些實施例中，受試者在投與細菌組成物之前尚未接收抗生素之劑量。在一些實施例中，受試者在投與本文提供的組成物之前尚未投與抗生素至少1天、至少2天、至少3天、至少5天、至少10天、至少15天、至少20天、至少25天、至少30天、至少60天、至少90天、至少120天、至少180天或至少360天。In some embodiments, the subject has not received a dose of an antibiotic before administration of the bacterial composition. In some embodiments, the subject has not been administered antibiotics for at least 1 day, at least 2 days, at least 3 days, at least 5 days, at least 10 days, at least 15 days, at least 20 days, At least 25 days, at least 30 days, at least 60 days, at least 90 days, at least 120 days, at least 180 days, or at least 360 days.

在一些實施例中，受試者可在細菌組成物之前或與細菌組成物並行地投與抗生素之一或多個劑量。抗生素可出於各種原因來投與。例如，抗生素可在投與本文提供的細菌組成物之前投與以自結腸及/或腸移除細菌物種。抗生素亦可投與來在癌症治療的狀況下抑制不需要的感染。在某些情況下，抗生素可作為用於傳染性疾病之治療方法投與。In some embodiments, the subject may be administered one or more doses of antibiotics before or concurrently with the bacterial composition. Antibiotics can be administered for a variety of reasons. For example, antibiotics can be administered prior to administration of the bacterial composition provided herein to remove bacterial species from the colon and / or intestines. Antibiotics can also be administered to suppress unwanted infections in the context of cancer treatment. In some cases, antibiotics can be administered as a treatment for infectious diseases.

在一些實施例中，受試者在細菌組成物之前投與抗生素之單劑量。在一些實施例中，受試者在細菌組成物之前投與抗生素之多劑量。在一些實施例中，受試者在細菌組成物之前投與抗生素之至少2、3、4、5個或更多個劑量。在一些實施例中，受試者在與細菌組成物實質上同時投與抗生素之劑量。可投與的抗生素之實例包括而不限於康黴素、建它黴素、黏菌素、甲硝噠唑、萬古黴素、氯林絲菌素、非達黴素及頭孢匹拉。診斷及預測方法 In some embodiments, the subject is administered a single dose of antibiotic prior to the bacterial composition. In some embodiments, the subject is administered multiple doses of antibiotics before the bacterial composition. In some embodiments, the subject is administered at least 2, 3, 4, 5, or more doses of antibiotics before the bacterial composition. In some embodiments, the subject is administered the dose of the antibiotic substantially simultaneously with the bacterial composition. Examples of antibiotics that can be administered include, but are not limited to, concomycin, gentamicin, colistin, metronidazole, vancomycin, clindamycin, fidaxomycin, and cefepira. Diagnosis and prediction methods

本文亦描述適用於判定受試者是否應接收治療的診斷方法(例如，伴隨式診斷)，該治療諸如如本文描述的組成物及/或本文描述的任何免疫查核點抑制劑。此種方法可用於診斷疾病、監視疾病之進程、評定用於疾病之治療之功效及/或識別適用於特定治療之患者。Also described herein are diagnostic methods (e.g., companion diagnostics) suitable for determining whether a subject should receive treatment, such as a composition as described herein and / or any immune checkpoint inhibitor described herein. Such methods can be used to diagnose a disease, monitor the progress of a disease, assess the efficacy of a treatment for a disease, and / or identify patients suitable for a particular treatment.

因此，本文描述的方法係基於自受試者獲得的樣本(例如，含有淋巴細胞之生物標本)中之標誌物之位準。在一些實施例中，該等方法涉及分析來自受試者的一或多個樣本中標誌物之存在及/或位準。Therefore, the methods described herein are based on the level of markers in a sample obtained from a subject (e.g., a biological specimen containing lymphocytes). In some embodiments, the methods involve analyzing the presence and / or level of a marker in one or more samples from a subject.

在一些實施例中，自受試者獲得的樣本中標誌物之位準可隨後與參考樣本或對照樣本比較以判定指示樣本中標誌物之量的值。在一些實施例中，標誌物之值係藉由將樣本中標誌物之位準與樣本中另一標誌物(例如，內部對照或內部標準)之位準比較來獲得。標誌物之值可與參考值比較以判定受試者是否患有疾病或有患疾病之風險。在一些實施例中，將標誌物之位準與標誌物之預定閾值比較，由此所得的偏差可指示受試者患有疾病。在一些實施例中，若標誌物之位準或值高於參考位準或值，則受試者可識別為患有疾病或有患疾病之風險，如本文所述。在一些實施例中，若標誌物之位準或值低於參考位準或值，則受試者可識別為患有疾病或有患疾病之風險，如本文所述。In some embodiments, the level of a marker in a sample obtained from a subject can then be compared to a reference or control sample to determine a value indicative of the amount of the marker in the sample. In some embodiments, the value of a marker is obtained by comparing the level of a marker in a sample to the level of another marker (eg, an internal control or internal standard) in the sample. The value of the marker can be compared with a reference value to determine whether the subject has a disease or is at risk of the disease. In some embodiments, the level of the marker is compared to a predetermined threshold of the marker, and the resulting deviation may indicate that the subject has a disease. In some embodiments, if the level or value of the marker is higher than the reference level or value, the subject can be identified as having a disease or at risk of having a disease, as described herein. In some embodiments, if the level or value of the marker is lower than the reference level or value, the subject can be identified as having a disease or at risk for the disease, as described herein.

在一些實施例中，將來自受試者的樣本中標誌物之位準與自同一受試者獲得的另一樣本中標誌物之位準比較，該另一樣本例如在不同時間自受試者獲得的樣本。在一些實施例中，將來自受試者的樣本中標誌物之位準與在較早時間，諸如在投與本文描述的任何組成物之前自受試者獲得的樣本中標誌物之位準比較。在一些實施例中，將來自受試者的樣本中標誌物之位準與在較晚時間、諸如在投與本文描述的任何組成物之後自受試者獲得的樣本中標誌物之位準比較。In some embodiments, the level of a marker in a sample from a subject is compared to the level of a marker in another sample obtained from the same subject, such as another sample from the subject at different times Obtained samples. In some embodiments, the level of a marker in a sample from a subject is compared to the level of a marker in a sample obtained from a subject at an earlier time, such as prior to administration of any of the compositions described herein. . In some embodiments, the level of a marker in a sample from a subject is compared to the level of the marker in a sample obtained from the subject at a later time, such as after administration of any of the compositions described herein .

在一些實施例中，若樣本中標誌物之位準或值相較於在投與本文描述的組成物之前獲得的來自受試者之樣本中標誌物之位準或值而言較高，則投與受試者本文描述的免疫查核點抑制劑及組成物。在一些實施例中，若樣本中標誌物之位準或值相較於在投與本文描述的組成物之前獲得的來自受試者之樣本中標誌物之位準或值而言較高，則受試者繼續涉及投與本文描述的免疫查核點抑制劑及組成物之療法。在一些實施例中，樣本中標誌物之位準或值在相較於在投與如本文描述的組成物之前樣本中標誌物之位準或值而言增強至少10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%、80%、85%、90%、95%、100%、110%、120%、130%、140%、150%、160%、170%、180%、190%或至少200%。In some embodiments, if the level or value of a marker in a sample is higher than the level or value of a marker in a sample from a subject obtained prior to administration of a composition described herein, then Subjects are administered the immune checkpoint inhibitors and compositions described herein. In some embodiments, if the level or value of a marker in a sample is higher than the level or value of a marker in a sample from a subject obtained prior to administration of a composition described herein, then Subjects continue to be involved in therapies that administer immune checkpoint inhibitors and compositions described herein. In some embodiments, the level or value of a marker in a sample is enhanced by at least 10%, 15%, 20% compared to the level or value of a marker in a sample before administration of a composition as described herein , 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 110 %, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190% or at least 200%.

在一些實施例中，若樣本中標誌物之位準或值相較於在投與本文描述的組成物之前獲得的來自受試者之樣本中標誌物之位準或值而言不增加(例如，相等或較低)，則中斷投與本文描述的免疫查核點抑制劑及組成物。在一些實施例中，若樣本中標誌物之位準或值相較於在投與本文描述的組成物之前獲得的來自受試者之樣本中標誌物之位準或值而言不增加(例如，相等或較低)，則在投與如本文描述的組成物之後重新分析本文描述的免疫查核點抑制劑及組成物之投與。在一些實施例中，樣本中標誌物之位準或值在相較於在投與如本文描述的組成物之前樣本中標誌物之位準或值而言減少至少10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%、80%、85%、90%、95%、100%、110%、120%、130%、140%、150%、160%、170%、180%、190%或至少200%。In some embodiments, the level or value of a marker in a sample does not increase compared to the level or value of a marker in a sample obtained from a subject prior to administration of a composition described herein (e.g., , Equal or lower), the administration of the immune checkpoint inhibitors and compositions described herein is discontinued. In some embodiments, the level or value of a marker in a sample does not increase compared to the level or value of a marker in a sample obtained from a subject prior to administration of a composition described herein (e.g., , Equal or lower), the administration of the immune checkpoint inhibitor and composition described herein is reanalyzed after the composition as described herein is administered. In some embodiments, the level or value of a marker in a sample is reduced by at least 10%, 15%, 20% compared to the level or value of a marker in a sample before administration of a composition as described herein , 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 110 %, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190% or at least 200%.

在一些實施例中，標誌物之位準係藉由分析標誌物(例如，蛋白質或核酸位準)之表現及/或表現標誌物之細胞類型來判定。此項技術中已知的任何方法可用以分析標誌物之表現及/或表現標誌物之細胞類型。In some embodiments, the level of a marker is determined by analyzing the performance of the marker (e.g., protein or nucleic acid level) and / or the type of cell in which the marker is expressed. Any method known in the art can be used to analyze the performance of the marker and / or the type of cell on which the marker is expressed.

本文亦提供基於自受試者獲得的樣本(例如，含有脾細胞之生物標本)中IFNγ產生之位準或程度的方法。在一些實施例中，該等方法涉及分析來自受試者的一或多個樣本中IFNγ產生之存在及/或位準。Also provided herein are methods based on the level or extent of IFNγ production in a sample obtained from a subject (e.g., a biological specimen containing spleen cells). In some embodiments, the methods involve analyzing the presence and / or level of IFNγ production in one or more samples from a subject.

在一些實施例中，自受試者獲得的樣本中IFNγ產生之位準可隨後與參考樣本或對照樣本比較以判定指示樣本中IFNγ產生之量的值。在一些實施例中，IFNγ產生之值係藉由將樣本中IFNγ產生之位準與樣本中另一分子(例如，內部對照或內部標準)之位準比較來獲得。IFNγ產生之值可與參考值比較以判定受試者是否患有疾病或有患疾病之風險。在一些實施例中，將IFNγ產生之位準與IFNγ產生之預定閾值比較，由此所得的偏差可指示受試者患有疾病。在一些實施例中，若IFNγ產生之位準或值高於參考位準或值，則受試者可識別為患有疾病或有患疾病之風險，如本文所述。在一些實施例中，若IFNγ產生之位準或值低於參考位準或值，則受試者可識別為患有疾病或有患疾病之風險，如本文所述。In some embodiments, the level of IFNγ production in a sample obtained from a subject can then be compared to a reference or control sample to determine a value indicative of the amount of IFNγ production in the sample. In some embodiments, the value of IFNγ production is obtained by comparing the level of IFNγ production in a sample with the level of another molecule (e.g., an internal control or internal standard) in the sample. The value produced by IFNγ can be compared with a reference value to determine whether the subject has a disease or is at risk of the disease. In some embodiments, the level of IFNγ production is compared to a predetermined threshold of IFNγ production, and the resulting deviation may indicate that the subject has a disease. In some embodiments, if the level or value of IFNγ production is higher than a reference level or value, the subject can be identified as having a disease or at risk for the disease, as described herein. In some embodiments, if the level or value of IFNγ production is lower than a reference level or value, the subject can be identified as having or at risk for a disease, as described herein.

在一些實施例中，將來自受試者的樣本中IFNγ產生之位準與自同一受試者獲得的另一樣本中IFNγ產生之位準比較，該另一樣本例如在不同時間自受試者獲得的樣本。在一些實施例中，將來自受試者的樣本中IFNγ產生之位準與在較早時間、諸如在投與本文描述的任何組成物之前自受試者獲得的樣本中IFNγ產生之位準比較。在一些實施例中，將來自受試者的樣本中IFNγ產生之位準與在較晚時間、諸如在投與本文描述的任何組成物之後自受試者獲得的樣本中IFNγ產生之位準比較。In some embodiments, the level of IFNγ production in a sample from a subject is compared to the level of IFNγ production in another sample obtained from the same subject, such as another sample from the subject at different times Obtained samples. In some embodiments, the level of IFNγ production in a sample from a subject is compared to the level of IFNγ production in a sample obtained from the subject at an earlier time, such as before administration of any of the compositions described herein. . In some embodiments, the level of IFNγ production in a sample from a subject is compared to the level of IFNγ production in a sample obtained from the subject at a later time, such as after administration of any of the compositions described herein .

在一些實施例中，若樣本中IFNγ產生之位準或值相較於在投與本文描述的組成物之前獲得的來自受試者之樣本中IFNγ產生之位準或值而言較高，則投與受試者本文描述的免疫查核點抑制劑及組成物。在一些實施例中，若樣本中IFNγ產生之位準或值相較於在投與本文描述的組成物之前獲得的來自受試者之樣本中IFNγ產生之位準或值而言較高，則受試者繼續涉及投與本文描述的免疫查核點抑制劑及組成物之療法。在一些實施例中，樣本中IFNγ產生之位準或值在相較於在投與如本文描述的組成物之前樣本中IFNγ產生之位準或值而言增強至少10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%、80%、85%、90%、95%、100%、110%、120%、130%、140%、150%、160%、170%、180%、190%或至少200%。In some embodiments, if the level or value of IFNγ production in a sample is higher than the level or value of IFNγ production in a sample from a subject obtained prior to administration of a composition described herein, then Subjects are administered the immune checkpoint inhibitors and compositions described herein. In some embodiments, if the level or value of IFNγ production in a sample is higher than the level or value of IFNγ production in a sample from a subject obtained prior to administration of a composition described herein, then Subjects continue to be involved in therapies that administer immune checkpoint inhibitors and compositions described herein. In some embodiments, the level or value of IFNγ production in the sample is enhanced by at least 10%, 15%, 20% compared to the level or value of IFNγ production in the sample before administration of a composition as described herein , 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 110 %, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190% or at least 200%.

在一些實施例中，若樣本中IFNγ產生之位準或值相較於在投與本文描述的組成物之前獲得的來自受試者之樣本中IFNγ產生之位準或值而言不增加(例如，相等或較低)，則中斷投與本文描述的免疫查核點抑制劑及組成物。在一些實施例中，若樣本中IFNγ產生之位準或值相較於在投與本文描述的組成物之前獲得的來自受試者之樣本中IFNγ產生之位準或值而言不增加(例如，相等或較低)，則在投與如本文描述的組成物之後重新分析本文描述的免疫查核點抑制劑及組成物之投與。在一些實施例中，樣本中IFNγ產生之位準或值在相較於在投與如本文描述的組成物之前樣本中IFNγ產生之位準或值而言減少至少10%、15%、20%、25%、30%、35%、40%、45%、50%、55%、60%、65%、70%、75%、80%、85%、90%、95%、100%、110%、120%、130%、140%、150%、160%、170%、180%、190%或至少200%。In some embodiments, the level or value of IFNγ production in a sample does not increase compared to the level or value of IFNγ production in a sample obtained from a subject prior to administration of a composition described herein (e.g., , Equal or lower), the administration of the immune checkpoint inhibitors and compositions described herein is discontinued. In some embodiments, the level or value of IFNγ production in a sample does not increase compared to the level or value of IFNγ production in a sample obtained from a subject prior to administration of a composition described herein (e.g., , Equal or lower), the administration of the immune checkpoint inhibitor and composition described herein is reanalyzed after the composition as described herein is administered. In some embodiments, the level or value of IFNγ production in the sample is reduced by at least 10%, 15%, 20% compared to the level or value of IFNγ production in the sample before administration of a composition as described herein , 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 110 %, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190% or at least 200%.

在一些實施例中，IFNγ產生之位準係藉由分析IFNγ(例如，蛋白質或核酸位準)之表現及/或產生IFNγ之細胞類型來判定。此項技術中已知的任何方法可用以分析IFNγ之表現及/或識別產生IFNγ之細胞類型。In some embodiments, the level of IFNγ production is determined by analyzing the performance of IFNγ (eg, protein or nucleic acid levels) and / or the type of cell that produces IFNγ. Any method known in the art can be used to analyze the expression of IFNγ and / or identify the type of cells that produce IFNγ.

對照位準亦可為預定位準或閾值。此種預定位準可表示未患有標靶疾病或無患標靶疾病風險的受試者群體中標誌物或IFNγ產生之位準。其亦可表示在患有標靶疾病之受試者群體中標誌物或IFNγ產生之位準。The control level may also be a predetermined level or a threshold. Such a predetermined level may indicate a level of production of a marker or IFNγ in a population of subjects who are not suffering from or at risk of a target disease. It can also indicate the level of marker or IFNγ production in a population of subjects with a target disease.

預定位準可採取各種形式。例如，其可為單一截止值，諸如中值或平均值。在一些實施例中，此種預定位準可基於比較群組來建立，諸如，其中一個限定群組已知為患有標靶疾病且另一限定群組已知為未患有標靶疾病。替代地，預定位準可為一範圍，例如，表示對照群體中代謝物之位準的一範圍。Pre-targeting can take various forms. For example, it may be a single cut-off value, such as a median or average. In some embodiments, such predetermined levels may be established based on comparison groups, such as where one defined group is known to have a target disease and the other defined group is known to have no target disease. Alternatively, the predetermined level may be a range, for example, a range representing the level of a metabolite in a control population.

如本文所使用的，「升高的位準」或「增加的位準」意味著標誌物或IFNγ產生之位準高於另一樣本中之參考值或位準，該另一樣本諸如在投與本文描述的任何組成物之前自受試者獲得的樣本。標誌物或IFNγ產生之升高的位準包括高於參考值或高於來自受試者之另一樣本中的位準例如1%、5%、10%、20%、30%、40%、50%、60%、70%、80%、90%、100%、150%、200%、300%、400%、500%或更多的標誌物或IFNγ產生之位準。在一些實施例中，測試樣本中標誌物或IFNγ產生之位準高於參考樣本中之位準或來自受試者的另一樣本中之位準至少1.1、1.2、1.3、1.4、15、l.6、l.7、l.8、l.9、2、2.5、3、3.5、4、4.5、5、5.5、6、7、8、9、10、50、100、150、200、300、400、500、1000、10000倍或更多。As used herein, "elevated level" or "increased level" means that the level of marker or IFNγ production is higher than a reference value or level in another sample, such as the Samples obtained from a subject with any of the compositions described herein. Increased levels of markers or IFNγ include levels higher than a reference value or higher than in another sample from a subject such as 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 300%, 400%, 500% or more markers or levels of IFNγ production. In some embodiments, the level of marker or IFNγ production in the test sample is at least 1.1, 1.2, 1.3, 1.4, 15, 1 higher than the level in the reference sample or in another sample from the subject. .6, l.7, l.8, l.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 50, 100, 150, 200, 300 , 400, 500, 1000, 10,000 times or more.

如本文所使用的，「降低的位準」意味著標誌物或IFNγ產生之位準高於另一樣本中之參考值或位準，該另一樣本諸如在投與本文描述的任何組成物之前自受試者獲得的樣本。標誌物或IFNγ產生之降低的位準包括低於參考值或來自受試者之另一樣本中的位準例如1%、5%、10%、20%、30%、40%、50%、60%、70%、80%、90%、100%、150%、200%、300%、400%、500%或更多的標誌物或IFNγ產生之位準。在一些實施例中，測試樣本中標誌物或IFNγ產生之位準低於參考樣本中標誌物或IFNγ產生之位準或來自受試者的另一樣本中之位準至少1.1、1.2、1.3、1.4、15、l.6、l.7、l.8、l.9、2、2.5、3、3.5、4、4.5、5、5.5、6、7、8、9、10、50、100、150、200、300、400、500、1000、10000倍或更多。As used herein, "reduced level" means that the level of production of a marker or IFNγ is higher than a reference value or level in another sample, such as before administration of any composition described herein A sample obtained from a subject. Markers or levels of IFNγ reduction include levels below the reference value or in another sample from the subject such as 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 300%, 400%, 500% or more markers or levels of IFNγ production. In some embodiments, the level of marker or IFNγ production in the test sample is at least 1.1, 1.2, 1.3, or less than the level of marker or IFNγ production in the reference sample or in another sample from the subject. 1.4, 15, l.6, l.7, l.8, l.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 50, 100, 150, 200, 300, 400, 500, 1000, 10,000 times or more.

本文描述的方法中識別的受試者可為適合治療的受試者，該治療諸如利用如本文描述的免疫查核點抑制劑及任何組成物之組合進行的治療。The subject identified in the methods described herein may be a subject suitable for treatment, such as treatment with a combination of an immune checkpoint inhibitor and any composition as described herein.

本文描述的檢定方法及套組亦可應用於評估用於諸如本文描述的彼等者之疾病的治療之功效，倘若存在標誌物或IFNγ產生之位準與此等疾病之間的相關性。例如，多個生物標本可自對其執行治療之受試者在該治療之前及之後或在該治療之過程期間收集。標誌物或IFNγ產生之位準可指示治療是否為有效的。The assays and kits described herein can also be applied to assess the efficacy of treatments for diseases such as those described herein, provided there is a correlation between the level of marker or IFNγ production and these diseases. For example, multiple biological specimens may be collected from a subject to whom treatment is performed before and after the treatment or during the course of the treatment. The level of marker or IFNγ production may indicate whether the treatment is effective.

若受試者係識別為對治療不敏感，則將較高劑量及/或頻率之組成物及/或免疫查核點抑制劑給藥投與至所識別的受試者。在一些實施例中，在對治療反應或無需進一步治療時，在所識別的受試者中維持、降低或停止該劑量或頻率之治療劑給藥。替代地，不同治療可應用於發現其對第一治療不敏感的受試者。If the subject is identified as insensitive to treatment, a higher dose and / or frequency of the composition and / or immune checkpoint inhibitor is administered to the identified subject. In some embodiments, the dose or frequency of therapeutic agent administration is maintained, reduced, or discontinued in the identified subject in response to treatment or without further treatment. Alternatively, different treatments may be applied to subjects who are found to be insensitive to the first treatment.

在其他實施例中，標誌物或IFNγ產生之值亦可依賴於識別可為例如可藉由投與本文描述的組成物治療之疾病。 篩選方法In other embodiments, the value produced by a marker or IFNγ may also depend on identifying a disease that can be treated, for example, by administering a composition described herein. Screening method

本文提供的為用於篩選細菌或來源於細菌之生理學活性物質以識別產生所要反應的細菌或其生理學活性物質之方法。例如，在一些實施例中，篩選方法係用於識別誘導產生CD8+ IFNγ之T細胞之活化的細菌或來源於細菌之生理學活性物質。在一些實施例中，篩選方法係用於識別誘導產生CD8+ IFNγ之T細胞之活化的細菌或來源於細菌之生理學活性物質。在一些實施例中，篩選方法係用於識別作為免疫刺激劑的細菌或來源於細菌之生理學活性物質。Provided herein are methods for screening bacteria or physiologically active substances derived from bacteria to identify the bacteria or physiologically active substances that produce the desired reaction. For example, in some embodiments, the screening method is used to identify activated bacteria that induce CD8 + IFNγ producing T cells or bacteria-derived physiologically active substances. In some embodiments, the screening method is used to identify activated bacteria that induce CD8 + IFNγ producing T cells or bacteria-derived physiologically active substances. In some embodiments, the screening method is used to identify a bacterium as an immunostimulant or a physiologically active substance derived from the bacterium.

本文亦提供用於篩選測試物質以識別誘導活化之物質的方法，該等物質誘導或惡化由產生CD8+ IFNγ之T細胞所引起的疾病。Also provided herein are methods for screening test substances to identify substances that induce activation that induce or worsen diseases caused by CD8 + IFNγ producing T cells.

一般而言，篩選方法可活體外(例如，使用細胞)或活體內(例如，使用非人類動物模型)執行。在一些實施例中，該等方法涉及將細胞群體(例如，腸上皮細胞、末梢血液單核細胞)與測試物質(例如，細菌或其生理學活性物質)接觸且評定反應。在一些實施例中，反應為所要細胞群體(例如，CD8+ IFNγT細胞)之數量及/或活性。In general, screening methods can be performed in vitro (e.g., using cells) or in vivo (e.g., using non-human animal models). In some embodiments, the methods involve contacting a population of cells (e.g., intestinal epithelial cells, peripheral blood mononuclear cells) with a test substance (e.g., bacteria or a physiologically active substance thereof) and assessing the response. In some embodiments, the response is the number and / or activity of the desired cell population (eg, CD8 + IFNγT cells).

在一些實施例中，該等方法涉及利用測試物質(例如，細菌或其生理學活性物質)接種非人類動物模型且評定反應。在一些實施例中，非人類動物模型攝取測試物質。在一些實施例中，反應為所要細胞群體(例如，CD8+ IFNγT細胞)之數量及/或活性。在一些實施例中，反應為疾病或其症狀之改良，或疾病或其症狀之誘導/惡化。In some embodiments, the methods involve inoculating a non-human animal model with a test substance (eg, a bacterium or a physiologically active substance thereof) and assessing the response. In some embodiments, the test substance is ingested by a non-human animal model. In some embodiments, the response is the number and / or activity of the desired cell population (eg, CD8 + IFNγT cells). In some embodiments, the response is an improvement in the disease or its symptoms, or an induction / exacerbation of the disease or its symptoms.

在一些實施例中，在本文描述的任何篩選方法中識別的細菌及/或來源於細菌之生理學活性物質可投與至受試者例如用於疾病之治療。套組 In some embodiments, the bacteria and / or bacteria-derived physiologically active substances identified in any of the screening methods described herein can be administered to a subject, for example, for the treatment of a disease. Set

本揭示內容亦提供適用於例如基於脾細胞中IFNγ產生之程度或位準來評估免疫系統活化之套組，其涉及將如本文描述的任何組成物投與至受試者。在一些實施例中，樣本可在投與本文描述的任何組成物之前、期間及/或之後自受試者獲得。The present disclosure also provides a kit suitable for assessing immune system activation based, for example, on the extent or level of IFNγ production in spleen cells, which involves administering any composition as described herein to a subject. In some embodiments, a sample may be obtained from a subject before, during, and / or after administration of any of the compositions described herein.

在一些實施例中，套組含有一或多種用於偵測及/或量測樣本中IFNγ產生之量的分子。在一些實施例中，偵測或量測IFNγ產生之量的分子可包含特異地結合至IFNγ之一或多種結合劑。在一些實施例中，結合劑為特異地結合至IFNγ之抗體。在一些實施例中，結合劑為報導基因系統之部分，諸如結合至IFNγ且誘導編碼報導基因分子之基因之表現的細胞上之受體。在一些實施例中，套組亦含有標準或對照樣本，可將自受試者獲得的樣本中IFNγ之量與該標準或對照樣本比較。In some embodiments, the kit contains one or more molecules for detecting and / or measuring the amount of IFNγ produced in a sample. In some embodiments, a molecule that detects or measures the amount of IFNγ produced may comprise one or more binding agents that specifically bind to IFNγ. In some embodiments, the binding agent is an antibody that specifically binds to IFNγ. In some embodiments, the binding agent is part of a reporter gene system, such as a receptor on a cell that binds to IFNγ and induces the expression of a gene encoding a reporter gene molecule. In some embodiments, the set also contains a standard or control sample, and the amount of IFNγ in a sample obtained from the subject can be compared to the standard or control sample.

在一些實施例中，套組可用於執行本文描述的任何伴隨式診斷方法。In some embodiments, the kit can be used to perform any of the accompanying diagnostic methods described herein.

在一些實施例中，套組含有一或多種用於偵測及/或量測本文描述的細菌物種之任一者或其組分之量或存在的分子。在一些實施例中，偵測或量測細菌菌株之量的分子可包含特異地結合至細菌菌株之一或多種結合劑。在一些實施例中，結合劑特異地結合至識別細菌物種的一或多種細菌物種之特徵。在一些實施例中，結合劑為特異地結合至本文描述的細菌物種中一或多者之核酸序列(諸如特定16S rRNA序列)的核酸。在一些實施例中，套組亦含有標準或對照樣本，可將自受試者獲得的樣本與該標準或對照樣本比較。In some embodiments, the kit contains one or more molecules for detecting and / or measuring the amount or presence of any of the bacterial species or components thereof described herein. In some embodiments, a molecule that detects or measures the amount of a bacterial strain may comprise one or more binding agents that specifically bind to the bacterial strain. In some embodiments, the binding agent specifically binds to a feature that identifies one or more bacterial species. In some embodiments, the binding agent is a nucleic acid that specifically binds to a nucleic acid sequence (such as a specific 16S rRNA sequence) of one or more of the bacterial species described herein. In some embodiments, the set also contains a standard or control sample, and a sample obtained from the subject can be compared to the standard or control sample.

本揭示內容亦提供適用於判定治療方法例如腫瘤療法之套組，其涉及在投與本文描述的任何組成物之前、期間及/或之後分析標誌物(例如，CD44、CD8、IFNγ、GzmB、gp70 MC38肽(KSPWFTTL；(SEQ ID NO:53))特異性TCR或抗原來源的配位體特異性TCR)之表現。本文亦提供包含用於利用免疫查核點抑制劑(例如，PD-1抑制劑)之腫瘤療法的伴隨式診斷之套組。This disclosure also provides a set suitable for use in determining therapeutic methods, such as oncology, which involves analyzing markers (e.g., CD44, CD8, IFNγ, GzmB, gp70 before, during and / or after administration of any of the compositions described herein Performance of MC38 peptide (KSPWFTTL; (SEQ ID NO: 53))-specific TCR or antigen-derived ligand-specific TCR). Also provided herein is a kit comprising companion diagnostics for tumor therapy using immunological checkpoint inhibitors (eg, PD-1 inhibitors).

在一些實施例中，套組包括一或多種用於分析或監視標誌物之表現位準的組分，該標誌物諸如CD44、CD8、IFNγ、GzmB或腫瘤抗原來源的配位體特異性TCR。在一些實施例中，標誌物係藉由偵測標誌物之存在，藉由量測標誌物之位準(量)及/或其上存在標誌物的特定細胞類型來分析。在一些實施例中，偵測或量測標誌物之量的分子可包含特異地結合至標誌物的一或多種結合劑。在一些實施例中，結合劑為特異地結合至標誌物之抗體。在一些實施例中，結合劑為特異地結合至標誌物之MHC單體集合體。In some embodiments, the kit includes one or more components for analyzing or monitoring the level of performance of a marker, such as CD44, CD8, IFNγ, GzmB, or ligand-specific TCR derived from a tumor antigen. In some embodiments, the marker is analyzed by detecting the presence of the marker, by measuring the level (amount) of the marker and / or the specific cell type on which the marker is present. In some embodiments, a molecule that detects or measures the amount of a marker may include one or more binding agents that specifically bind to the marker. In some embodiments, the binding agent is an antibody that specifically binds to a marker. In some embodiments, the binding agent is a collection of MHC monomers that specifically binds to a marker.

在一些實施例中，標誌物係藉由偵測編碼標誌物之核酸的存在，藉由量測編碼標誌物之核酸之位準(量)，及/或其中表現編碼標誌物之核酸的特定細胞類型。在一些實施例中，套組包括一或多種用於從自受試者獲得的樣本分離核酸(例如，RNA)的試劑。In some embodiments, the marker is by detecting the presence of the nucleic acid encoding the marker, by measuring the level (amount) of the nucleic acid encoding the marker, and / or the specific cell in which the nucleic acid encoding the marker is expressed Types of. In some embodiments, the kit includes one or more reagents for isolating nucleic acids (eg, RNA) from a sample obtained from a subject.

在一些實施例中，套組進一步包含用於偵測藥劑與樣本中之標靶(例如，IFNγ、細菌物種)之結合的偵測劑(例如，結合至結合劑之抗體)。偵測劑可共軛至標記。在一些實施例中，偵測劑為特異地結合至結合劑之至少一者的抗體。在一些實施例中，結合劑包含可識別且藉由偵測劑直接或間接結合的標記。In some embodiments, the kit further comprises a detection agent (e.g., an antibody bound to a binding agent) for detecting binding of the agent to a target (e.g., IFNγ, bacterial species) in the sample. The detector can be conjugated to a label. In some embodiments, the detection agent is an antibody that specifically binds to at least one of the binding agents. In some embodiments, the binding agent comprises a label that can be identified and bound directly or indirectly by a detection agent.

在一些實施例中，套組可進一步包括用於投與至受試者的一或多種治療劑及/或組成物。例如，在一些實施例中，套組可包括一或多種免疫查核點抑制劑(例如，PD-1抑制劑、PD-L1抑制劑、CTLA-4抑制劑)。在一些實施例中，套組可包括包含本文描述的細菌菌株中之一或多者的組成物。In some embodiments, the kit may further include one or more therapeutic agents and / or compositions for administration to a subject. For example, in some embodiments, a kit can include one or more immune checkpoint inhibitors (eg, PD-1 inhibitors, PD-L1 inhibitors, CTLA-4 inhibitors). In some embodiments, a kit can include a composition comprising one or more of the bacterial strains described herein.

在一些實施例中，套組可用於篩選細菌或來源於細菌之物質，例如篩選產生CD8+ IFNγ之T細胞之活化。在一些實施例中，套組包括細胞，諸如細胞系之細胞。在一些實施例中，細胞為腸上皮細胞、末梢血液單核細胞。In some embodiments, the kits can be used to screen for bacteria or bacterial-derived materials, such as for activation of T cells that produce CD8 + IFNγ. In some embodiments, the set includes cells, such as cells of a cell line. In some embodiments, the cells are intestinal epithelial cells, peripheral blood mononuclear cells.

在一些實施例中，套組或裝置進一步包括支撐構件。在一些實施例中，支撐構件為膜，諸如硝基纖維素膜、聚偏二氟乙烯(polyvinylidene fluoride；PVDF)膜或乙酸纖維膜。在一些實例中，免疫檢定可呈西方墨點檢定格式或側向流檢定格式。In some embodiments, the kit or device further includes a support member. In some embodiments, the support member is a film, such as a nitrocellulose film, a polyvinylidene fluoride (PVDF) film, or an acetate fiber film. In some examples, the immunoassay may be in a Western blot assay format or a lateral flow assay format.

在一些實施例中，支撐構件為多孔板，諸如ELISA板。在一些實施例中，本文描述的免疫檢定可在高生產量平臺上進行。在一些實施例中，例如，24、48、96、384或更大數孔板之多孔板可用於高生產量偵測檢定。In some embodiments, the support member is a multiwell plate, such as an ELISA plate. In some embodiments, the immunoassays described herein can be performed on a high-throughput platform. In some embodiments, for example, multi-well plates of 24, 48, 96, 384 or larger multiwell plates can be used for high throughput detection assays.

在套組或偵測裝置中，結合劑中之一或多者可固定在支撐構件上，該支撐構件可為膜、珠粒、滑塊或多孔板。選擇用於免疫檢定之適當支撐構件將取決於各種因素，諸如樣本數量及偵測自共軛至第二藥劑之標記釋放的信號的方法。In the kit or detection device, one or more of the binding agents may be fixed on a supporting member, which may be a membrane, a bead, a slider, or a multiwell plate. Choosing the appropriate support member for the immunoassay will depend on a variety of factors, such as the number of samples and the method of detecting the signal released from the conjugate to the marker of the second agent.

套組亦可包含如本文描述的一或多種緩衝液但不限於塗佈緩衝液、阻斷緩衝液、洗滌緩衝液及/或停止緩衝液。Kits may also include one or more buffers as described herein, but are not limited to coating buffers, blocking buffers, washing buffers, and / or stopping buffers.

在一些實施例中，套組可包含根據本文描述的任何方法之使用說明書。關於套組之使用的說明書通常包括關於每一組分之量及用於執行本文描述的檢定方法之適合條件的資料。套組中之組分可呈單位劑量、散裝包裝(例如，多劑量包裝)或亞單位劑量。在本揭示內容之套組中供應的說明書典型地為標記或包裝插頁(例如，套組中包括的紙片)上之書面說明書，但機器可讀指令(例如，在磁性或光學儲存碟上進行的指令)亦為可接受的。In some embodiments, a kit can include instructions for use according to any of the methods described herein. The instructions for use of the kits generally include information on the amount of each component and suitable conditions for performing the assays described herein. The components in the kit can be in unit dose, bulk packaging (e.g., multi-dose packaging), or subunit dosage. The instructions supplied in the set of this disclosure are typically written instructions on a label or package insert (e.g., a piece of paper included in the set), but machine-readable instructions (e.g., on magnetic or optical storage discs) Directive) is also acceptable.

標記或包裝插頁指示套組用於評估免疫系統活化之位準，選擇治療，及/或診斷目的。指令可提供來用於實踐本文描述的任何方法。The label or package insert indicates that the kit is used to assess the level of activation of the immune system, select treatment, and / or diagnostic purposes. Instructions may be provided for practicing any of the methods described herein.

本揭示內容之套組處於適合的包裝中。適合的包裝包括但不限於小瓶、瓶子、罐、可撓性包裝(例如，密封麥拉或塑膠袋)及類似物。The kit of the present disclosure is in a suitable package. Suitable packaging includes, but is not limited to, vials, bottles, cans, flexible packaging (eg, sealed mylar or plastic bags), and the like.

套組可視情況提供另外的組分，諸如說明資訊，諸如對照及/或標準或參考樣本。通常，套組包含容器及容器上或與容器相關聯的標記或包裝插頁。在一些實施例中，本揭示內容提供包含上文所述的套組之內容物之製品。The kit may optionally provide additional components, such as explanatory information, such as controls and / or standards or reference samples. Generally, a kit contains a container and a label or packaging insert on or associated with the container. In some embodiments, the disclosure provides an article of manufacture comprising the contents of a kit as described above.

下文表1提供用於本文揭示的實驗之組成物的序列識別符編號(SEQ ID NO)。與所指示菌株最接近的細菌物種係以屬-種提出。亦提供識別為最接近相關屬種的與每一屬種相關聯的16S rDNA序列。對準百分比提出所指示菌株之序列與來自最接近屬種之序列之間的一致性百分比及對準長度。最接近相關物種之GenBank登錄號提供於最後一列中。 Table 1 below provides the sequence identifier number (SEQ ID NO) of the composition used in the experiments disclosed herein. The bacterial species closest to the indicated strains are presented as genera-species. A 16S rDNA sequence associated with each genus identified as closest to the related genus is also provided. Percent alignment shows the percent identity and alignment length between the sequence of the indicated strain and the sequence from the closest genus. The GenBank accession number closest to the relevant species is provided in the last column.

本文描述的細菌菌株之16S rDNA或其部分之核酸序列在下文提供： SEQ ID NO:1 菌株1 2G5_糞考拉桿菌_LN998073 SEQ ID NO:2 菌株2 1A6_潰瘍梭桿菌_KR822463 SEQ ID NO:3 菌株3 1B11_多利擬桿菌_CP011531 SEQ ID NO:4 菌株4 2G1_單形擬桿菌_NR_112945 SEQ ID NO:5 菌株5 2B1_罕見小球菌屬4_3_54A2FAA_NZ-ACWW00000000 SEQ ID NO:6 菌株6 2A6_Paraprevotella xylaniphila_AB331897SEQ ID NO:7 菌株7 2F11_約氏副擬桿菌_AB261128SEQ ID NO:8 菌株8 1E7_別樣桿菌屬JC136_NZ-CAEG00000000 SEQ ID NO:9 菌株9 1H9_戈登副擬桿菌_AB470343 SEQ ID NO:10 菌株10 1C1_黏真桿菌_AB595134 SEQ ID NO:11 菌株11 2G9_狄氏副擬桿菌_HE974920 SEQ ID NO:12 菌株12 2B7_解纖維素擬桿菌_NR_112933 SEQ ID NO:13 菌株13 2C1_克拉氏擬桿菌_AB490801 SEQ ID NO:14 菌株14 1B4_厭氧棒狀菌屬3_2_56FAA_NZ-ACWB00000000SEQ ID NO:15 菌株15 2A3_塞爾氏擬桿菌_AY608696 SEQ ID NO:16 菌株16 2A12_脆弱擬桿菌_CR626927 SEQ ID NO:17 菌株17 1A2_單形擬桿菌_AB247141 SEQ ID NO:18 菌株18 2B11_埃氏擬桿菌_NR_112935 SEQ ID NO:19 菌株19 2D2_梭菌屬TM-40_AB249652SEQ ID NO:20 菌株20 2E8_古氏副擬桿菌_NR_113076SEQ ID NO:21 菌株21 1H8_擬桿菌屬AR29_AF139525 SEQ ID NO:22 菌株22 ＞3F2-PREMIX.fasta SEQ ID NO:23 菌株2 3 ＞1G1_3-PREMIX.fasta SEQ ID NO:24菌株24 ＞1E6_27Fmod-PREMIX_Length_957SEQ ID NO:25菌株25 ＞1F3_27Fmod-PREMIX.fastaSEQ ID NO:26菌株26 1A1_27Fmod-PREMIX_Length_998 SEQ ID NO:27 對應於LN998073之16S RNA序列 SEQ ID NO:28 對應於KR822463之16S RNA序列 SEQ ID NO:29 對應於CP011531之16S RNA序列 SEQ ID NO:30 對應於NR112945之16S RNA序列 SEQ ID NO:31 對應於KM098109之16S RNA序列 SEQ ID NO:32 對應於NR113078之16S RNA序列 SEQ ID NO:33 對應於NR041464之16S RNA序列 SEQ ID NO:34 對應於LT223566之16S RNA序列 SEQ ID NO:35 對應於NR112835之16S RNA序列 SEQ ID NO:36 對應於NR113248之16S RNA序列 SEQ ID NO:37 對應於NR041342之16S RNA序列 SEQ ID NO:38 對應於NR112933之16S RNA序列 SEQ ID NO:39 對應於NR112893之16S RNA序列 SEQ ID NO:40 對應於HE974918之16S RNA序列 SEQ ID NO:41 對應於NR043016之16S RNA序列 SEQ ID NO:42 對應於AB618791之16S RNA序列 SEQ ID NO:43 對應於AB215083之16S RNA序列 SEQ ID NO:44 對應於NR112935之16S RNA序列 SEQ ID NO:45 對應於AB249652之16S RNA序列 SEQ ID NO:46 對應於NR113076之16S RNA序列 SEQ ID NO:47 對應於NR112944之16S RNA序列 SEQ ID NO:48 對應於JX519760之16S RNA序列 SEQ ID NO:49 對應於AJ311620之16S RNA序列 SEQ ID NO:50 對應於EF564278之16S RNA序列 SEQ ID NO:51 對應於KT156811之16S RNA序列 SEQ ID NO:52 對應於HM008265之16S RNA序列The nucleic acid sequence of the 16S rDNA or a portion of a bacterial strain described herein is provided below: SEQ ID NO: 1 Strain 1 2G5_Koala Faecium_LN998073 SEQ ID NO: 2 Strain 2 1A6_ Clostridium ulcerans_KR822463 SEQ ID NO: 3 Strain 3 1B11_Bacterial dorisi_CP011531 SEQ ID NO: 4 Strain 4 2G1_Bacteroides monomorphum_NR_112945 SEQ ID NO: 5 Strain 5 2B1_ Rare Micrococcus 4_3_54A2FAA_NZ-ACWW00000000 SEQ ID NO: 6 Strain 6 2A6_Paraprevotella xylaniphila_AB331897 SEQ ID NO: 7 Strain 7 2F11_Pseudomonas yojei_AB261128 SEQ ID NO: 8 Strain 8 1E7_Isobacterium JC136_NZ-CAEG00000000 SEQ ID NO: 9 Strain 9 1H9_Pseudomonas gordon_AB470343 SEQ ID NO: 10 Strain 10 1C1_mycobacteria_AB595134 SEQ ID NO: 11 Strain 11 2G9_Pseudomonas dickens_HE974920 SEQ ID NO: 12 Strain 12 2B7_Bacteriolytic cellulose_NR_112933 SEQ ID NO: 13 Strain 13 2C1_Bacterium clarkii_AB490801 SEQ ID NO: 14 Strain 14 1B4_Corynebacterium 3_2_56FAA_NZ-ACWB00000000 SEQ ID NO: 15 Strain 15 2A3_Bacteroides seleno_AY608696 SEQ ID NO: 16 Strain 16 2A12_Bacteroides fragilis_CR626927 SEQ ID NO: 17 Strain 17 1A2_Bacteroides haemolyticus_AB247141 SEQ ID NO: 18 Strain 18 2B11_Bacteroides escherichia_NR_112935 SEQ ID NO: 19 Strain 19 2D2_Clostridium TM-40_AB249652 SEQ ID NO: 20 Strain 20 2E8_Pseudomonas gutii_NR_113076 SEQ ID NO: 21 Strain 21 1H8_Bacteroides AR29_AF139525 SEQ ID NO: 22 Strain 22> 3F2-PREMIX.fasta SEQ ID NO: 23 Strain 2 3 ＞ 1G1_3-PREMIX.fasta SEQ ID NO: 24 Strain 24> 1E6_27Fmod-PREMIX_Length_957 SEQ ID NO: 25 strain 25 ＞ 1F3_27Fmod-PREMIX.fasta SEQ ID NO: 26 strain 26 1A1_27Fmod-PREMIX_Length_998 SEQ ID NO: 27 16S RNA sequence corresponding to LN998073 SEQ ID NO: 28 16S RNA sequence corresponding to KR822463 SEQ ID NO: 29 16S RNA sequence corresponding to CP011531 SEQ ID NO: 30 16S RNA sequence SEQ ID NO corresponding to NR112945 NO: 31 16S RNA sequence corresponding to KM098109 SEQ ID NO: 32 16S RNA sequence corresponding to NR113078 SEQ ID NO: 33 16S RNA sequence corresponding to NR041464 SEQ ID NO: 34 16S RNA sequence corresponding to LT223566 SEQ ID NO: 35 16S RNA sequence corresponding to NR112835 SEQ ID NO: 36 16S RNA sequence corresponding to NR113248 SEQ ID NO: 37 16S RNA sequence corresponding to NR041342 SEQ ID NO: 38 16S RNA sequence corresponding to NR112933 SEQ ID NO: 39 corresponding 16S RNA sequence at NR112893 SEQ ID NO: 40 corresponds to 16S RNA sequence of HE974918 SEQ ID NO: 41 corresponds to 16S RNA sequence of NR043016 SEQ ID NO: 42 corresponds to 16S RNA sequence of AB618791 SEQ ID NO: 43 corresponds to AB215083 16S RNA sequence SEQ ID NO: 44 corresponds to NR112935 16S RNA sequence SEQ ID NO: 45 corresponds to AB249652 16S RNA sequence SEQ ID NO: 46 corresponds to NR113076 16S RNA sequence SEQ ID NO: 47 corresponds to NR112944 16S RNA sequence SEQ ID NO: 48 corresponds to JX519760-1 6S RNA sequence SEQ ID NO: 49 corresponds to 16S RNA sequence of AJ311620 SEQ ID NO: 50 corresponds to 16S RNA sequence of EF564278 SEQ ID NO: 51 corresponds to 16S RNA sequence of KT156811 SEQ ID NO: 52 corresponds to 16S RNA of HM008265 sequence

所關注的另外的序列在下文提供： SEQ ID NO:54 H81A6_16S_核糖體_RNA SEQ ID NO:55 H82F11_16S_核糖體_RNA SEQ ID NO:56 H82A6_16S_核糖體_RNA SEQ ID NO:57 H82G9_16S_核糖體_RNA SEQ ID NO:58 H81E7_16S_核糖體_RNA SEQ ID NO:59 H81C1_16S_核糖體_RNA SEQ ID NO:60 H81B11_16S_核糖體_RNASEQ ID NO:61 H81H9_16S_核糖體_RNASEQ ID NO:62 H82B1_16S_核糖體_RNASEQ ID NO:63 H82G1_16S_核糖體_RNA SEQ ID NO:64 H82G5_16S_核糖體_RNA Additional sequences of interest are provided below: SEQ ID NO: 54 H81A6_16S_ribosomal_RNA SEQ ID NO: 55 H82F11_16S_ribosomal_RNA SEQ ID NO: 56 H82A6_16S_ribosomal_RNA SEQ ID NO: 57 H82G9_16S_ribosomal_RNA SEQ ID NO: 58 H81E7_16S_ribosomal_RNA SEQ ID NO: 59 H81C1_16S_ribosomal_RNA SEQ ID NO: 60 H81B11_16S_ribosomal_RNA SEQ ID NO: 61 H81H9_16S_ribosomal_RNA SEQ ID NO: 62 H82B1_16S_ribosomal_RNA SEQ ID NO: 63 H82G1_16S_ribosomal_RNA SEQ ID NO: 64 H82G5_16S_ribosomal_RNA

本發明之應用不限於以下描述中闡述或圖式中說明的構造細節及組件佈置。本發明能夠有其他實施例且以各種方式實踐或進行。此外，本文使用的片語及術語係出於描述之目的且不應視為限制性的。本文中「包括」、「包含」或「具有」、「含有」、「涉及」及其變化形式意味著涵蓋其後所列的項目其等效物以及另外的項目。The invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced or carried out in various ways. In addition, the phrases and terms used herein are for description purposes and should not be considered limiting. "Including," "including," or "having," "containing," "involving," and variations thereof are intended to cover equivalents to the items listed thereafter, as well as additional items.

除非本文另外定義，否則結合本揭示內容使用的科學及技術術語應具有一般技藝人士通常所理解的含義。另外，除非上下文另外需要，否則單數術語應包括複數且複數術語應包括單數。本揭示內容之方法及技術通常根據此項技術中熟知的習知方法執行。通常，本文描述的結合生物化學、酵素學、分子及細胞生物學、微生物學、病毒學、細胞或組織培養、遺傳學及蛋白質及核酸化學使用的命名法為此項技術中熟知及常用的彼等命名法。除非另外指示，否則本揭示內容之方法及技術通常係根據此項技術中熟知且如在遍及本說明書引用及論述的各種一般及更特定參考文獻中描述的習知方法執行。Unless otherwise defined herein, scientific and technical terms used in connection with the present disclosure shall have meanings as commonly understood by one of ordinary skill in the art. In addition, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. The methods and techniques of this disclosure are generally performed according to conventional methods well known in the art. In general, the nomenclatures used in this context that combine biochemistry, enzymes, molecular and cellular biology, microbiology, virology, cell or tissue culture, genetics, and protein and nucleic acid chemistry are well known and commonly used in the art. And other nomenclature. Unless otherwise indicated, the methods and techniques of the present disclosure are generally performed according to well-known methods well known in the art and as described in various general and more specific references cited and discussed throughout this specification.

本發明進一步藉由以下實例說明，該等實例決不應揭示為進一步限制。遍及本申請案引用的所有參考文獻(包括文獻參考、經頒與專利、公開專利申請案及同在申請中之專利申請案)之全部內容係據此以引用方式明確地併入，尤其對上文參考的教示內容如此。然而，任何參考文獻之引用皆不意欲承認參考文獻係先前技術。 實例 實例1：CD8+ T細胞誘導細菌混合物(cocktail)之識別The invention is further illustrated by the following examples, which should by no means be disclosed as further limitations. The entire contents of all references cited in this application (including literature references, issued patents, published patent applications, and patent applications in the same application) are hereby expressly incorporated by reference, in particular the above The teachings of the text refer to this. However, the citation of any reference is not intended to acknowledge that the reference is prior art. Examples Example 1: Identification of CD8 + T-cell-induced bacterial cocktails

在無特定病原(specific-pathogen free；SPF)條件下保持的擁有駐留微生物群的C57BL/6小鼠具有豐富的IFNγ+CD8+ T細胞，而在無菌小鼠之腸內固有層中發現明顯少數的IFNγ+CD8+ T細胞(參見第1圖)。此指示腸管微生物群誘導IFNγ+CD8+ T細胞之累積。IFNγ+CD8+ T細胞之子集亦表現CD103以及顆粒酶B (參見第2A圖)，從而暗示子集為組織駐留的記憶T細胞。第3A圖展示在自Charles River Laboratories Inc.及日本SLC Inc.購買的SPF C57BL/6小鼠中發現相較於自CLEA Japan Inc.購買的SPF C57BL/6小鼠及在RIKEN中繁殖的小鼠而言顯著小數量之IFNγ+CD8+ T細胞。當來自Charles River Laboratories Inc.之SPF C57BL/6小鼠與CLEA小鼠一起在同一籠中共同收容時，在自Charles River Laboratories Inc.遞送的小鼠中觀察到IFNγ+CD8+ T細胞之增加(第4A圖及第4B圖)。此發現強烈地支援以下假設：在小鼠微生物群中存在特定微生物物種，其在腸內誘導並累積IFNγ+CD8+ T細胞。C57BL / 6 mice with a resident microbiota maintained under specific-pathogen free (SPF) conditions are rich in IFNγ + CD8 + T cells, while significantly fewer are found in the lamina propria of sterile mice IFNγ + CD8 + T cells (see Figure 1). This indicates that the gut microbiota induces the accumulation of IFNγ + CD8 + T cells. A subset of IFNγ + CD8 + T cells also showed CD103 and granzyme B (see Figure 2A), suggesting that the subset is memory T cells in which the tissue resides. Figure 3A shows that SPF C57BL / 6 mice purchased from Charles River Laboratories Inc. and SLC Inc. of Japan were found compared to SPF C57BL / 6 mice purchased from CLEA Japan Inc. and mice that were propagated in RIKEN. Significantly small numbers of IFNγ + CD8 + T cells. When SPF C57BL / 6 mice from Charles River Laboratories Inc. were co-hosted with CLEA mice in the same cage, an increase in IFNγ + CD8 + T cells was observed in mice delivered from Charles River Laboratories Inc. (No. 4A and 4B). This finding strongly supports the hypothesis that there is a specific microbial species in the mouse microbiota that induces and accumulates IFNγ + CD8 + T cells in the intestine.

接著，調查人類腸管微生物群是否含有能夠誘導IFNγ+CD8+ T細胞之微生物。自六位健康人類志願者(A~F)收集糞便樣本。樣本係個別地經口投與至保持在無菌隔離器中之無菌C57BL/6小鼠中(每組五或六隻小鼠)。在糞便樣本之經口接種之後四週，犧牲小鼠，且收穫小腸及結腸且藉由FACS調查IFNγ+CD8+ T細胞。Next, investigate whether the human intestinal microbiota contains microorganisms capable of inducing IFNγ + CD8 + T cells. Fecal samples were collected from six healthy human volunteers (A ~ F). Samples were individually orally administered to sterile C57BL / 6 mice (five or six mice per group) kept in a sterile isolator. Four weeks after oral inoculation of stool samples, mice were sacrificed, and the small intestine and colon were harvested and IFNγ + CD8 + T cells were investigated by FACS.

如第5A圖及第5B圖所示，結腸IFNγ+CD8+ T細胞係在利用自供體B收集的糞便樣本接種的小鼠中最顯著地誘導。在利用供體B糞便樣本接種的小鼠之中，吾等選擇展現最高頻率之IFNγ+CD8+ T細胞的小鼠(後文稱為『小鼠B#5』)。為濃縮負責IFNγ+CD8+ T細胞誘導之微生物，自小鼠B#5收集盲腸內容物且接種至另一無菌小鼠中。隨後在利用或不利用安比西林、甲硝噠唑、鏈黴素或泰黴素的情況下經口投與小鼠飲用水(每組五隻小鼠)。替代地，利用3%氯仿處理小鼠B#5之盲腸內容物且經口接種至另外五隻無菌小鼠(『B#5+Chrolo』)中。第6A圖及第6B圖展示安比西林治療因小鼠B#5微生物群增強結腸固有層IFNγ+CD8+ T細胞之誘導，而其他抗生素治療或氯仿治療因小鼠B#5微生物群減少誘導IFNγ+CD8+ T細胞之能力。As shown in Figures 5A and 5B, colonic IFNγ + CD8 + T cell lines were most significantly induced in mice inoculated with stool samples collected from donor B. Among the mice inoculated with a donor B stool sample, we selected mice that exhibited the highest frequency of IFNγ + CD8 + T cells (hereinafter referred to as "mouse B # 5"). To concentrate the microorganisms responsible for IFNγ + CD8 + T cell induction, the cecum contents were collected from mouse B # 5 and inoculated into another sterile mouse. Mice were subsequently orally administered drinking water with or without ampicillin, metronidazole, streptomycin, or teithromycin (five mice per group). Alternatively, the cecum contents of mouse B # 5 were treated with 3% chloroform and orally inoculated into another five sterile mice ("B # 5 + Chrolo"). Figures 6A and 6B show that ampicillin treatment induces induction of IFNγ + CD8 + T cells in colonic lamina propria due to the B # 5 microbiota of mice, while other antibiotic treatment or chloroform treatment induces IFNγ + due to reduced B # 5 microbiota CD8 + T cells.

第7A圖及第7B圖展示利用小鼠B#5微生物群接種且利用/不利用抗生素或氯仿治療的小鼠之腸內內容物之操作分類單位(operational taxonomic unit；OTU)分析。自展現最高頻率之IFNγ+CD8+ T細胞的兩種B#5+AMP小鼠(小鼠B#5+AMP-2及小鼠B#5+AMP-3)收集盲腸內容物且在厭氧腔室中培養。拾取304個菌落且16S rRNA基因之測序揭露分離了26種菌株。二十一種菌株係選自26種菌株，排除5種包括在B#5+Chrolo小鼠之微生物群中(因此預測為誘導IFNγ+CD8+ T細胞所不必要的)的菌株。21種菌株之混合物經口接種至無菌小鼠中且觀察到IFNγ+CD8+ T細胞之強烈誘導(第8A圖及第8B圖)。藉由21種菌株誘導的IFNγ+CD8+ T細胞亦表現CD103且IFNγ+CD8+ T細胞之一部分亦表現顆粒酶B(第9A圖及第9B圖)。具有與IFNγ+CD8+ T細胞最高相關性之11種菌株之混合物係亦接種至GF小鼠中。11種菌株之混合物(11混合)經口強烈誘導IFNγ+CD8+ T細胞，甚至在相較於21種菌株混合物(21混合)時如此(第10A圖及第10B圖)。下文表2中提供與11混合中每一菌株具有最高同源性的細菌物種之識別。 實例1A：11種菌株之混合物(組成物A)之進一步表徵Figures 7A and 7B show operational taxonomic unit (OTU) analysis of intestinal contents of mice inoculated with the mouse B # 5 microbiota and treated with or without antibiotics or chloroform. The cecum contents were collected from two B # 5 + AMP mice (mouse B # 5 + AMP-2 and mouse B # 5 + AMP-3) showing the highest frequency of IFNγ + CD8 + T cells and placed in the anaerobic cavity Room culture. Picking 304 colonies and sequencing the 16S rRNA gene revealed that 26 strains were isolated. Twenty-one strains were selected from 26 strains, excluding 5 strains included in the microbiome of B # 5 + Chrolo mice (thus predicted to be unnecessary to induce IFNγ + CD8 + T cells). A mixture of 21 strains was orally inoculated into sterile mice and strong induction of IFNγ + CD8 + T cells was observed (Figures 8A and 8B). IFNγ + CD8 + T cells induced by 21 strains also showed CD103 and a part of IFNγ + CD8 + T cells also showed granzyme B (Figures 9A and 9B). A mixture of 11 strains with the highest correlation with IFNγ + CD8 + T cells was also inoculated into GF mice. A mixture of 11 strains (Mixed 11) orally strongly induces IFNγ + CD8 + T cells, even when compared to a mixture of 21 strains (Mixed 21) (Figures 10A and 10B). Identification of the bacterial species with the highest homology to each strain in the 11 mix is provided in Table 2 below. Example 1A: Further characterization of a mixture of 11 strains (composition A)

表2之菌株係藉由16S序列之重新測序及藉由整體基因組測序來進一步表徵。進一步表徵之結果見於表2A中。 實例2：CD8+ T細胞誘導細菌混合物之進一步表徵The strains of Table 2 were further characterized by resequencing of the 16S sequence and by sequencing the entire genome. The results of further characterization are shown in Table 2A. Example 2: Further characterization of a bacterial mixture induced by CD8 + T cells

第11圖展示自B#5+AMP小鼠之盲腸內容物分離的展現高頻率之IFNγ+CD8+ T細胞的二十六種菌株。在26種菌株之中，11種菌株(「11混合」)與IFNγ+CD8+ T細胞之頻率正相關。因此，該些11種菌株係選擇來用於進一步實驗，且11種菌株之混合物(「11混合」)係接種至無菌小鼠中(參見表2)。利用11混合之菌落形成導致結腸IFNγ+CD8+ T細胞之強烈誘導(第10A圖、第10B圖、第12A圖及第12B圖)，而其他10種菌株(「10混合」)相較於藉由11混合誘導的位準微弱地誘導IFNγ+CD8+ T細胞(第12A圖及第12B圖)。利用17 Treg誘導細菌菌株之混合物接種的小鼠(參見，例如，WO2013/080561；Atarashi等人，Nature (2013) 500 (7461)：232-236；Narushima等人 Gut Microbes (2014)5(3)：333-339)不累積IFNγ+CD8+ T細胞(第12A圖及第12B圖)。Figure 11 shows twenty-six strains of IFNγ + CD8 + T cells exhibiting high frequency isolated from the cecum contents of B # 5 + AMP mice. Of the 26 strains, 11 strains ("11 mix") were positively correlated with the frequency of IFNγ + CD8 + T cells. Therefore, these 11 strains were selected for further experiments, and a mixture of 11 strains ("11 mix") was inoculated into sterile mice (see Table 2). Colony formation using 11 mixes resulted in strong induction of colonic IFNγ + CD8 + T cells (Figures 10A, 10B, 12A, and 12B), while the other 10 strains ("10 mixes") compared to The 11 mixed induction level weakly induced IFNγ + CD8 + T cells (Figures 12A and 12B). Mice inoculated with a mixture of 17 Treg-inducing bacterial strains (see, eg, WO2013 / 080561; Atarashi et al., Nature (2013) 500 (7461): 232-236; Narushima et al. Gut Microbes (2014) 5 (3) : 333-339) does not accumulate IFNγ + CD8 + T cells (Figures 12A and 12B).

使用16S rRNA基因序列之系統比較展示11菌株混合物(亦稱為「11混合」)由7種屬於擬桿菌之菌株(「7種菌株」)及4種非擬桿菌：2種梭菌、1種梭桿菌及1種Selenomonadales (「4種菌株」)組成(參見第13圖及表3)。A systematic comparison using 16S rRNA gene sequences shows that a mixture of 11 strains (also known as "11 mixtures") consists of 7 strains belonging to Bacteroides ("7 strains") and 4 non-Bacteroides: 2 Clostridium, 1 Composition of Clostridium and 1 Selenomonadales ("4 strains") (see Figure 13 and Table 3).

利用4種非擬桿菌菌株之混合物(「4混合」)進行的接種導致結腸IFNγ+CD8+ T細胞之強烈累積，其相當於利用11混合選殖的小鼠中觀察到的結腸IFNγ+CD8+ T細胞之位準。對比而言，利用7種擬桿菌菌株(「7混合」)進行的菌落形成微弱地誘導IFNγ+CD8+ T細胞(第14A圖及第14B圖)。Inoculation with a mixture of 4 non-Bacteroides strains ("4 mixes") resulted in a strong accumulation of colonic IFNγ + CD8 + T cells, which is equivalent to colonic IFNγ + CD8 + T cells observed in mice colonized with 11 mixes Standard. In contrast, colony formation using 7 types of Bacteroides strains ("7 mix") weakly induced IFNγ + CD8 + T cells (Figures 14A and 14B).

第47圖展示實驗之重複，其展示11混合比7混合或4混合更有效。第47圖中展示的實驗之資料獲得強烈的統計學支援。Figure 47 shows a repetition of the experiment, which shows that 11 mix is more effective than 7 mix or 4 mix. The experimental data shown in Figure 47 received strong statistical support.

下文表3中提供與4混合中每一菌株具有最高同源性的細菌物種之識別。 實例3：CD8+ T細胞誘導細菌混合物之抗癌特性Identification of the bacterial species with the highest homology to each strain in the 4 mix is provided in Table 3 below. Example 3: Anticancer properties of bacterial mixtures induced by CD8 + T cells

調查利用11混合進行的菌落形成是否可增強抗癌劑免疫反應，使用皮下腫瘤模型。自第-7天至第2天，經由飲用水，利用抗生素之混合物(1 g/L安比西林、0.5 g/L萬古黴素、1 g/L甲硝噠唑及1 g/L新黴素)治療SPF小鼠。在第0天，將MC38結腸癌細胞系(每只小鼠3x105 個細胞)皮下地注射至小鼠之右側腹中。在第2天停止抗生素治療，且以來自SPF小鼠之糞便微生物群並在第3天在與或不與11混合進行混合的情況下胃管灌食小鼠。對於11混合治療組而言，每週兩次或三次利用11混合胃管灌食小鼠直至實驗結束。對於抗PD-1抗體(Ab)治療組而言，在第3天、第5天及第9天利用200 μg之抗PD1單株Ab (純系J43)腹膜內注射小鼠。使用測徑規量測腫瘤大小且腫瘤體積係測定為長度x寬度2 x 0.5。To investigate whether colony formation using the 11 mix can enhance the immune response of anticancer agents, a subcutaneous tumor model was used. From day -7 to day 2, use a mixture of antibiotics (1 g / L ampicillin, 0.5 g / L vancomycin, 1 g / L metronidazole, and 1 g / L neomycin via drinking water) ) Treat SPF mice. On day 0, the MC38 colon carcinoma cell line (3x10 5 cells per mouse) were injected subcutaneously into the right flank of mice. Antibiotic treatment was discontinued on day 2 and the mice were gavage with fecal microbiota from SPF mice and mixed with or without mixing with 11 on day 3. For the 11 mixed treatment group, mice were fed with the 11 mixed gastric tube twice or three times a week until the end of the experiment. For the anti-PD-1 antibody (Ab) treatment group, mice were injected intraperitoneally with 200 μg of an anti-PD1 single Ab (pure line J43) on the 3rd, 5th, and 9th days. Tumor size was measured using a caliper and tumor volume was measured as length x width 2 x 0.5.

單獨利用11混合進行的治療(亦即，無抗PD1 Ab)顯著地抑制MC38腫瘤生長(參見第15圖)。11混合及抗PD1 Ab之組合展現對腫瘤細胞之生長的最強抑制效應(參見第15圖)。利用11混合及抗PD1 Ab進行的治療導致IFNγ+CD8+ T細胞在MC38腫瘤質塊中之升高的累積(參見第16A圖及第16B圖)。腫瘤中IFNγ+CD8+ T細胞之子集表現對gp70p15E604-611 (KSPWFTTL；SEQ ID NO :53) (其為MC38之免疫顯性抗原決定基)特異的T細胞受體(第17A圖)。此外，IFNγ+CD8+ T細胞之子集表現CD44及顆粒酶B，從而暗示在腫瘤中累積的IFNγ+CD8+ T細胞包括腫瘤特異性及記憶類型的細胞毒性CD8+ T細胞(參見第17A圖及第17B圖)。對IFNγ+CD4 T細胞之效應展示於第18圖中。Treatment with the 11 mix alone (ie, without anti-PD1 Ab) significantly inhibited MC38 tumor growth (see Figure 15). The combination of 11 mix and anti-PD1 Ab showed the strongest inhibitory effect on tumor cell growth (see Figure 15). Treatment with 11-blend and anti-PD1 Ab resulted in increased accumulation of IFNγ + CD8 + T cells in MC38 tumor mass (see Figures 16A and 16B). A subset of IFNγ + CD8 + T cells in tumors showed T cell receptors specific for gp70p15E604-611 (KSPWFTTL; SEQ ID NO: 53) (which is the immunodominant epitope of MC38) (Figure 17A). In addition, a subset of IFNγ + CD8 + T cells showed CD44 and granzyme B, suggesting that IFNγ + CD8 + T cells accumulated in tumors include tumor-specific and memory-type cytotoxic CD8 + T cells (see Figures 17A and 17B) ). The effect on IFNγ + CD4 T cells is shown in Figure 18.

利用11混合進行的經口接種導致產生IFNγ之脾細胞之數量增加，甚至在不存在腫瘤抗原刺激的情況下如此(參見第19圖)。Oral inoculation with Mix 11 resulted in an increase in the number of splenocytes producing IFNγ, even in the absence of tumor antigen stimulation (see Figure 19).

該些結果展示在與/不與抗PD1 Ab組合的情況下利用11混合進行的治療全身地活化對腫瘤細胞反應的CD8 T細胞。 實例4：與CTLA-4免疫查核點抑制劑組合的CD8+ T細胞誘導細菌混合物之抗癌特性These results show that treatment with 11 mix with / without anti-PD1 Ab systemically activates CD8 T cells that respond to tumor cells. Example 4: Anti-cancer properties of a bacterial mixture induced by CD8 + T cells in combination with a CTLA-4 immune checkpoint inhibitor

為調查利用11混合與免疫查核點抑制劑CTLA4組合進行的菌落形成是否可增強抗癌劑免疫反應，使用皮下腫瘤模型(第24圖)。利用抗生素之混合物治療小鼠5天(自第-21天至第-16天)，繼之以兩天時期以洗去抗生素。在第-14天，將MC38結腸癌細胞系(每只小鼠3x105 個細胞)皮下地注射至小鼠之右側腹中。將動物隨機分至以下治療組中： 第1組：無抗生素，無治療(提供對MC38腫瘤模型之標準進程的參考)； 第2組：抗生素預治療，無治療(提供對利用抗生素預治療之MC38腫瘤模型之進程的參考)； 第3組：11混合單一療法(在第25圖及第26圖中稱為AAM1)； 第8組：抗CTLA-4抗體(9H10)及11混合(在第25圖及第26圖中稱為AAM1)組合； 第9組：抗CTLA-4抗體(9H10)單一療法。To investigate whether colony formation using the combination of 11 and CTLA4, an immune checkpoint inhibitor, could enhance the anti-cancer agent immune response, a subcutaneous tumor model was used (Figure 24). Mice were treated with the antibiotic mixture for 5 days (from day -21 to day -16), followed by a two-day period to wash off the antibiotic. At -14 days, MC38 colon carcinoma cell line (3x10 5 cells per mouse) were injected subcutaneously into the right flank of mice. Animals were randomly assigned to the following treatment groups: Group 1: No antibiotics, no treatment (providing reference to the standard course of the MC38 tumor model); Group 2: Antibiotic pretreatment, no treatment (providing the use of antibiotic pretreatment Reference for the progression of the MC38 tumor model); Group 3: 11 mixed monotherapy (referred to as AAM1 in Figures 25 and 26); Group 8: Anti-CTLA-4 antibody (9H10) and 11 mixed (in Section Figure 25 and Figure 26 are called AAM1) combination; Group 9: Anti-CTLA-4 antibody (9H10) monotherapy.

細菌混合物治療亦在第-14天開始且每兩週4次地投與。對於接收CTLA-4免疫查核點抑制劑之群組而言，一旦腫瘤體積達到大致100 mm3 (100-150 mm3 )，即開始治療。在第1天、第4天及第7天投與抗CTLA-4抗體。在實驗過程中評定小鼠之重量及存活。量測腫瘤大小及體積。腫瘤量測 Bacterial mixture treatment was also started on day -14 and administered 4 times every two weeks. For groups receiving CTLA-4 immune checkpoint inhibitors, treatment will begin once the tumor volume reaches approximately 100 mm 3 (100-150 mm 3 ). Anti-CTLA-4 antibodies were administered on days 1, 4, and 7. Mice were evaluated for weight and survival during the experiment. Measure tumor size and volume. Tumor measurement

單獨接收抗CTLA-4抗體之小鼠組(第9組)相較於對照小鼠具有稍微減少的腫瘤生長。11混合(在第25圖中稱為「AAM1」)及抗CTLA-4抗體之組合(第8組)相較於11混合自身並相較於抗CTLA-4抗體自身顯著地減少腫瘤生長。參見第25圖。第27圖中展示個別小鼠之腫瘤體積圖表。存活 The group of mice receiving anti-CTLA-4 antibody alone (Group 9) had slightly reduced tumor growth compared to control mice. The combination of 11 mix (referred to as "AAM1" in Figure 25) and anti-CTLA-4 antibody (group 8) significantly reduced tumor growth compared to 11 mix itself and compared to the anti-CTLA-4 antibody itself. See Figure 25. The tumor volume chart of individual mice is shown in Figure 27. Survive

單獨接收抗CTLA-4抗體之小鼠組相較於對照小鼠具有稍微增加的存活。11混合自身對存活無影響。11混合(在第26圖中稱為「AAM1」)及抗CTLA-4抗體之組合顯著地增強所治療小鼠之存活(第8組)。參見第26圖。 實例5：與抗PD1抗體組合的CD8+ T細胞誘導細菌混合物之抗癌特性The group of mice receiving anti-CTLA-4 antibodies alone had slightly increased survival compared to control mice. 11 mixing itself has no effect on survival. The combination of 11 mix (referred to as "AAM1" in Figure 26) and anti-CTLA-4 antibody significantly enhanced the survival of the treated mice (Group 8). See Figure 26. Example 5: Anti-cancer properties of a CD8 + T cell-induced bacterial mixture in combination with an anti-PD1 antibody

為調查利用4混合或11混合與免疫查核點抑制劑抗PD1組合進行的菌落形成是否可在不存在抗生素預治療及先前植入的情況下增強抗癌劑免疫反應，在第-14天，將MC38結腸癌細胞系(每只小鼠3x105 個細胞)皮下地注射至小鼠之右側腹中(參見第28圖)。將動物隨機分至以下治療組中： 第1組：無治療； 第3組：11混合單一療法(在第28圖及第29圖中稱為「AAM1」)； 第4組：4混合單一療法(在第28圖及第29圖中稱為「AAM2」)； 第5組：抗PD1抗體(RMP1-14)單一療法； 第6組：抗PD1抗體(RMP1-14)及11混合(在第28圖及第29圖中稱為「AAM1」)組合；及 第7組：抗PD1抗體(RMP1-14)及4混合(在第28圖及第29圖中稱為「AAM2」)組合。To investigate whether colony formation using a combination of 4 or 11 mix with immune checkpoint inhibitor anti-PD1 can enhance anti-cancer agent immune response in the absence of antibiotic pretreatment and previous implantation, on day -14, the MC38 colon carcinoma cell line (3x10 5 cells per mouse) were injected subcutaneously into the right flank of mice (see Figure 28). Animals were randomly assigned to the following treatment groups: Group 1: No treatment; Group 3: 11 mixed monotherapy (referred to as "AAM1" in Figures 28 and 29); Group 4: 4 mixed monotherapy (Referred to as "AAM2" in Figures 28 and 29); Group 5: anti-PD1 antibody (RMP1-14) monotherapy; Group 6: anti-PD1 antibody (RMP1-14) and 11 mixed (in Figure 28 and Figure 29 are called "AAM1") combination; and Group 7: anti-PD1 antibody (RMP1-14) and 4 mixed (called "AAM2" in Figure 28 and Figure 29) combination.

治療在第1天開始(腫瘤體積大致100-150 mm3 )。細菌混合物治療及抗PD1抗體係每兩週兩次地投與。在實驗過程中評定小鼠之重量及存活。量測腫瘤大小及體積。腫瘤量測 Treatment started on day 1 (tumor volume was approximately 100-150 mm 3 ). Bacterial mixture treatment and anti-PD1 antibody system are administered twice every two weeks. Mice were evaluated for weight and survival during the experiment. Measure tumor size and volume. Tumor measurement

單獨利用抗PD1抗體或與4混合或11混合組合進行的治療相較於無治療的情況導致腫瘤生長之減少。第30圖展示在實例5之實驗中所治療的個別小鼠之腫瘤體積圖表(對照、11混合；αPD-1 Ab；11混合+ αPD-1 Ab)。在11混合+ αPD-1 Ab治療組(底部右圖面)中，在多個動物中腫瘤體積不增加。第32圖展示在實例5之實驗中所治療的個別小鼠之腫瘤體積圖表(對照、4混合；αPD-1 Ab；4混合+ αPD-1 Ab)。在4混合+ αPD-1 Ab治療組(底部右圖面)中，在多個動物中腫瘤體積不增加。存活 Treatment with anti-PD1 antibodies alone or in combination with 4 or 11 mixtures resulted in a reduction in tumor growth compared to untreated cases. Figure 30 shows a tumor volume chart of individual mice treated in the experiment of Example 5 (control, 11 mixed; αPD-1 Ab; 11 mixed + αPD-1 Ab). In the 11 mixed + αPD-1 Ab treatment group (bottom right panel), tumor volume did not increase in multiple animals. Figure 32 shows tumor volume charts for individual mice treated in the experiment of Example 5 (control, 4 mixed; αPD-1 Ab; 4 mixed + αPD-1 Ab). In the 4 mixed + αPD-1 Ab treatment group (bottom right panel), tumor volume did not increase in multiple animals. Survive

第31圖中展示針對對照、11混合；PD-1 Ab；及11混合+ PD-1 Ab群組之存活資料。11混合及αPD-1 Ab之組合在相較於11混合自身或αPD-1 Ab自身時展示增加的存活。Figure 31 shows survival data for the control, 11 mixed; PD-1 Ab; and 11 mixed + PD-1 Ab groups. The combination of 11 mix and αPD-1 Ab showed an increased survival when compared to 11 mix itself or αPD-1 Ab itself.

第33圖中展示在對照、4混合；αPD-1 Ab；4混合+ αPD-1 Ab、11混合及11混合+ αPD-1 Ab群組中的小鼠之組合存活資料。4混合及αPD-1 Ab之組合及11混合及αPD-1抗體之組合兩者在相較於αPD-1 Ab自身時展示增加的存活。 實例6：在黑素瘤模型與抗PD1抗體組合的CD8+ T細胞誘導細菌混合物之抗癌特性Figure 33 shows the combined survival data for mice in the control, 4 mixed; αPD-1 Ab; 4 mixed + αPD-1 Ab, 11 mixed, and 11 mixed + αPD-1 Ab groups. Both the 4 mix and the combination of αPD-1 Ab and the 11 mix and the combination of αPD-1 antibody showed increased survival when compared to the αPD-1 Ab itself. Example 6: Anti-cancer properties of a mixture of bacteria induced by CD8 + T cells in a melanoma model with anti-PD1 antibody

黑素瘤植入小鼠模型用於評估11混合與PD-1抗體組合在黑素瘤之治療中之功效。如第34圖及第35圖中之時間線所示，小鼠自第-3天至第2天接收抗生素(安比西林、萬古黴素、甲硝噠唑及新黴素：「AVMN」)。在第0天，利用7x105 Braf Pten黑素瘤細胞植入小鼠。小鼠分組為以下治療組： -無特定病原(Specific Pathogen Free；SPF)糞便； -SPF糞便+抗PD1抗體； -SPF糞便+ 11混合；及 -SPF糞便+ 11混合+抗PD1抗體。A mouse model of melanoma implantation was used to evaluate the efficacy of the combination of 11 and PD-1 antibody in the treatment of melanoma. As shown by timelines in Figures 34 and 35, mice received antibiotics (ampicillin, vancomycin, metronidazole, and neomycin: "AVMN") from day -3 to day 2. On day 0, mice were implanted with 7x10 5 Braf Pten melanoma cells. Mice were grouped into the following treatment groups:-Specific Pathogen Free (SPF) stool;-SPF stool + anti-PD1 antibody;-SPF stool + 11 mix; and-SPF stool + 11 mix + anti-PD1 antibody.

在第3天、第6天及第9天，投與小鼠來自由日本SLC獲得的無特定病原(specific-pathogen free；SPF)小鼠之SLC SPF糞便(SLC SPF糞便)、抗PD1抗體(第34圖及第35圖中時間線上之箭頭)及/或11混合(第34圖及第35圖中時間線上帶星號之箭頭)。藉由胃管灌食每週2或3次將11混合投與至所指示小鼠組。接收抗PD1抗體及11混合之組合的小鼠相較於其他小鼠組具有減少的腫瘤體積(第34圖)、腫瘤面積(第35圖)及腫瘤重量(第36圖)。On days 3, 6, and 9, mice were administered SLC SPF stool (SLC SPF stool) and anti-PD1 antibody (SLC SPF stool) from specific-pathogen free (SPF) mice obtained from Japanese SLC. Figure 34 and Figure 35 arrows on the timeline) and / or 11 mixed (Figure 34 and Figure 35 arrows with timeline on the timeline). 11 were mixedly administered to the indicated mouse group by gastric tube gavage 2 or 3 times a week. Mice receiving the combination of anti-PD1 antibody and 11 had a reduced tumor volume (Figure 34), tumor area (Figure 35), and tumor weight (Figure 36) compared to other mouse groups.

在第22天及第24天自由小鼠獲得的腫瘤分離淋巴細胞且使用對細胞標誌物之抗體染色，該等細胞標誌物包括CD3、TCRβ、CD8、CD4、IFNγ、顆粒酶及IL-17。利用11混合及抗PD1抗體組合進行的治療導致黑素瘤腫瘤中IFNγ+CD8+ T細胞之升高的累積。第37A圖-第37C圖及第38圖。在此實驗中，在小鼠組之間，IFNγ+GzmB+細胞、Th1細胞、Th17細胞或Treg細胞之數量不存在顯著差異。第39A圖-第39D圖。Tumors were obtained from free mice on day 22 and day 24 and lymphocytes were isolated and stained with antibodies to cell markers including CD3, TCRβ, CD8, CD4, IFNγ, granzyme, and IL-17. Treatment with a combination of 11 and an anti-PD1 antibody combination resulted in increased accumulation of IFNγ + CD8 + T cells in melanoma tumors. Figure 37A-Figure 37C and Figure 38. In this experiment, there was no significant difference in the number of IFNγ + GzmB + cells, Th1 cells, Th17 cells, or Treg cells between the mouse groups. Figure 39A-Figure 39D.

該些結果展示利用11混合與抗PD1抗體組合進行的治療全身地活化黑素瘤中之CD8 T細胞。 實例7：在無特定病原(Specific-Pathogen Free；SPF)小鼠中之CD8 T細胞誘導These results show that treatment with a combination of 11 and an anti-PD1 antibody systemically activates CD8 T cells in melanoma. Example 7: CD8 T cell induction in Specific-Pathogen Free (SPF) mice

評估藉由11混合細菌混合物誘導CD8 T細胞之實驗參數。相較於無菌小鼠，用於此研究的動物為無特定病原小鼠(specific pathogen free mice；SPF mice)。Assess experimental parameters for the induction of CD8 T cells by 11 mixed bacterial mixtures. Compared to sterile mice, the animals used for this study were specific pathogen free mice (SPF mice).

如第40圖所示，小鼠分組為以下治療組： -11混合多劑量； -AVMN + SPF糞便； -AVMN + SPF糞便+ 11混合單劑量；及 -AVMN + SPF糞便+ 11混合多劑量。As shown in Figure 40, mice were grouped into the following treatment groups: -11 mixed multiple doses;-AVMN + SPF stool;-AVMN + SPF stool + 11 mixed single dose; and-AVMN + SPF stool + 11 mixed multiple doses.

所指示小鼠組自第-5天至第-1天在其飲用水中接收抗生素(安比西林、萬古黴素、甲硝噠唑及新黴素：「AVMN」)。在第0天在利用或不利用11混合的情況利用SPF糞便接種小鼠。對於接收多劑量之11混合的群組而言，亦在第3天、第7天、第10天、第14天、第17天、第21天、第24天及第28天於水中投與細菌混合物。The indicated group of mice received antibiotics (ampicillin, vancomycin, metronidazole, and neomycin: "AVMN") in their drinking water from day -5 to day -1. Mice were inoculated with SPF feces on day 0 with or without 11 mixes. For groups receiving 11 doses of multiple doses, they were also administered in water on days 3, 7, 10, 14, 14, 17, 21, 24, and 28. Bacterial mixture.

在第22天及第24天自小鼠分離淋巴細胞且使用對細胞標誌物之抗體染色，該等細胞標誌物包括CD3、TCRβ、CD8、CD4、IFNγ、顆粒酶及IL-17。接收抗生素預治療及多劑量之11混合的小鼠展示IFNγ+CD8+ T細胞之增強位準。第41A圖-第41C圖。接收抗生素預治療及多劑量之11混合的小鼠亦已增強細胞之CD8T細胞群體中CD103+ IFNγ+細胞之位準(第42A圖)且稍微增強Th17細胞之位準(第42B圖)。在小鼠組之間，Th1細胞之數量不存在顯著差異。(第42C圖)。該些資料展示11混合可誘導在以複雜背景中誘導CD8+ T細胞：無特定病原小鼠(相較於無菌小鼠)。 實例8：轉錄因子BATF3之作用Lymphocytes were isolated from mice on days 22 and 24 and stained with antibodies to cell markers including CD3, TCRβ, CD8, CD4, IFNγ, granzyme, and IL-17. Mice receiving 11 pre-treatments with antibiotics and multiple doses of the mixed exhibited enhanced levels of IFNγ + CD8 + T cells. Figure 41A-Figure 41C. Mice receiving the antibiotic pretreatment and multiple doses of 11 mix also enhanced the level of CD103 + IFNγ + cells in the CD8T cell population of cells (Figure 42A) and slightly enhanced the level of Th17 cells (Figure 42B). There was no significant difference in the number of Th1 cells between the mouse groups. (Fig. 42C). These data demonstrate that 11 mixes can induce CD8 + T cells in a complex background: pathogen-free mice (compared to sterile mice). Example 8: The role of the transcription factor BATF3

將11混合投與至具有BATF3轉錄因子之小鼠及不具有BATF3轉錄因子之小鼠。不具有轉錄因子BATF3之小鼠對藉由11混合進行的CD8 T細胞誘導不敏感。(第43A圖及第43B圖)。刺激產生IFN-γ之CD8及Th1細胞可能需要CD103-CD11b樹狀細胞。藉由11混合混合物誘導Th17細胞不依賴於BAFT3狀態。(第43C圖)。第43圖及第44圖展示來自實例8之實驗的結果。實驗展示11混合需要BATF3來誘導CD8-T細胞。不需要BATF3來誘導Th17。 實例9：李氏菌屬感染小鼠之治療。11 was mixedly administered to mice with a BATF3 transcription factor and mice without a BATF3 transcription factor. Mice without the transcription factor BATF3 were not sensitive to CD8 T cell induction by the 11 mix. (Figures 43A and 43B). CD103-CD11b dendritic cells may be required to stimulate CD8 and Th1 cells that produce IFN-γ. Induction of Th17 cells by a mixed mixture of 11 does not depend on the BAFT3 state. (Fig. 43C). Figures 43 and 44 show the results from the experiment of Example 8. The experiments showed that the 11 mix required BATF3 to induce CD8-T cells. BATF3 is not required to induce Th17. Example 9: Treatment of Listeria infected mice.

因為IFNg+CD8+ T細胞已經報道在控制細胞內病原體中起到關鍵作用，所以評估在多個給藥方案中利用11菌株混合物進行的口服補充是否可增加針對單核球增多性李氏菌感染之宿主保護性免疫。經由飲用水利用AVMN (安比西林、萬古黴素、甲硝噠唑、新黴素)治療SPF小鼠5天。在抗生素之一天洗去之後執行11混合之多次口服投與(4次)。為重構複合微生物群，將來自SPF小鼠之糞便微生物群與11混合之第一次投與一起引入。隨後在第0天利用單核球增多性李氏菌經口感染小鼠。判定小鼠之糞便李氏菌屬CFU及體重。利用11混合進行的治療顯著地減少腸管內腔之單核球增多性李氏菌菌落形成(第45圖)且維持小鼠之體重(第46圖)。因此，11菌株混合物之投與可提供針對細胞內傳染性病原體之保護性免疫。 實例10：藉由11混合誘導的CD8 T細胞之定域Because IFNg + CD8 + T cells have been reported to play a key role in controlling intracellular pathogens, it was evaluated whether oral supplementation using a mixture of 11 strains in multiple dosing regimens could increase the risk of infection against Listeria monocytogenes Host protective immunity. SPF mice were treated with AVMN (ampicillin, vancomycin, metronidazole, neomycin) via drinking water for 5 days. Multiple oral administrations of 11 mixes (4 times) were performed after the antibiotic was washed away on one day. To reconstitute the complex microbiota, the fecal microbiota from SPF mice was introduced with the first administration of 11 mixed. Mice were then orally infected with Listeria monocytogenes on day 0. The feces of the mice were determined for CFU and body weight. Treatment with the 11 mix significantly reduced the formation of Listeria monocytogenes Listeria colonies in the lumen of the intestine (Figure 45) and maintained the weight of the mice (Figure 46). Therefore, administration of a mixture of 11 strains can provide protective immunity against intracellular infectious pathogens. Example 10: Localization of CD8 T cells induced by 11 mix

將11混合投與至正常健康小鼠(亦即，在其他情況下不受應力的小鼠)。針對CD8陽性T細胞之存在來調查小鼠中之各種器官及隔室。如第48圖所示，11混合之CD8陽性T細胞誘導效應受限於腸/腸道(SI =小腸、CIEL =結腸上皮內淋巴細胞、LN =淋巴結)。 實例11：固有層樹狀細胞之子集之選擇性及暫時活化。11 was mixedly administered to normal healthy mice (ie, mice that were otherwise unstressed). Various organs and compartments in mice were investigated for the presence of CD8-positive T cells. As shown in Figure 48, the induction effect of the mixed CD8 positive T cells of 11 is limited to the intestine / intestinal tract (SI = small intestine, CIEL = colon intraepithelial lymphocytes, LN = lymph nodes). Example 11: Selective and temporary activation of a subset of lamina dendritic cells.

因為CD8細胞可經由樹狀細胞之某些亞類來活化，所以在投與11混合之後調查固有層CD11b-CD103+樹狀細胞之數量及活化狀態。如第49圖所示，11混合之投與不改變固有層CD11b-CD103+樹狀細胞子集之比例。Because CD8 cells can be activated via certain subclasses of dendritic cells, the number and activation status of CD11b-CD103 + dendritic cells in the lamina propria were investigated after administration of 11 mix. As shown in Fig. 49, the administration of 11 mixes did not change the proportion of the lamina propria CD11b-CD103 + dendritic cell subset.

亦調查活化之暫時性/動力學。利用11混合選殖GF小鼠達1、2、3及4週。結腸LP及MLN樹狀細胞(dendritic cell；DC)/巨噬細胞子集之頻率不受利用11混合進行的菌落形成的影響。然而，在結腸LP DC (而非MLN DC)上、尤其在結腸LP CD103+ DC子集(亦即，Batf3依賴性DC子集)上的MHC I類之表現藉由利用11混合進行的菌落形成顯著地增強。MHC I類表現之上調在菌落形成之後1週最強烈地發生。(參見第50圖-第54圖) 不限於特定機制，CD8陽性T細胞之誘導可能主要歸因於增殖而非抗原特異性之重新分化。The transient / kinetics of activation were also investigated. GF mice were colonized with 11 mixes for 1, 2, 3, and 4 weeks. The frequency of colonic LP and MLN dendritic cell (DC) / macrophage subsets was not affected by colony formation using the 11 mix. However, the performance of MHC class I on colonic LP DCs (not MLN DCs), especially on a subset of colonic LP CD103 + DCs (i.e., Batf3-dependent DC subsets), was significant through colony formation using 11 mix Ground enhancement. MHC class I performance up-regulation occurred most strongly 1 week after colony formation. (See Figure 50-Figure 54) Without being limited to a specific mechanism, the induction of CD8-positive T cells may be mainly due to proliferation rather than antigen-specific redifferentiation.

Ki67染色揭露：CD8陽性T細胞之擴張在第1週發生，其伴隨結腸LP中IFNg+ CD8+ T之增加(參見第55圖)。CD103染色揭露：在菌落形成後1週的所誘導IFNg+ CD8+ T主要為CD103陰性，且CD103+ IFNg+ CD8 T (組織駐留記憶表現型CD8+ T)逐漸增加(參見第56圖及第57圖)。Ki67 staining revealed that expansion of CD8-positive T cells occurred at week 1, which was accompanied by an increase in IFNg + CD8 + T in colonic LP (see Figure 55). CD103 staining revealed that the induced IFNg + CD8 + T at 1 week after colony formation was mainly CD103 negative, and CD103 + IFNg + CD8 T (CD8 + T resident memory phenotype) gradually increased (see Figure 56 and Figure 57).

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隨附圖式不意欲按比例描繪。圖式僅為說明性的且對實現本揭示內容而言並非必需。為達清晰之目的，並非所有組件可在每一圖式中標記。在圖式中：The accompanying drawings are not intended to be drawn to scale. The drawings are merely illustrative and are not required to implement the present disclosure. For purposes of clarity, not all components may be labeled in every drawing. In the scheme:

第1A圖及第1B圖展示利用淋巴細胞進行的實驗之資料，該等淋巴細胞係自SPF及無菌(germ-free；GF)小鼠之小腸(small intestine；SI)及結腸黏膜固有層分離且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第1A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現。(第1B圖) CD3、TCRβ及CD8+細胞內之IFNγ陽性細胞之百分比的彙總資料。每一圖表表示個別小鼠。** P ＜0.01(學生t檢驗)。Figures 1A and 1B show the data of experiments using lymphocytes, which were separated from the small intestine (SI) and colonic lamina propria of SPF and germ-free (GF) mice and Stimulation with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Figure 1A) The expression of CD8 and IFNγ by gating CD3 and TCRβ positive cells in representative mice. (Figure 1B) Summary data of the percentage of IFNγ positive cells in CD3, TCRβ and CD8 + cells. Each graph represents an individual mouse. ** P <0.01 (student's t-test).

第2A圖及第2B圖展示利用淋巴細胞進行的實驗之資料，該等淋巴細胞係自SPF及無菌小鼠之小腸黏膜固有層分離且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8、CD103、IFNγ及GzmB且藉由流動式細胞測量術分析。(第2A圖) 藉由代表性小鼠之閘控CD8 T細胞進行的IFNγ及CD103 (上列)或GzmB (下列)之表現。(第2B圖) CD3、TCRβ及CD8+細胞內之每一IFNγ陽性細胞餾分之百分比的彙總資料。每一圖表表示個別小鼠。* P ＜0.05 (學生t檢驗)。Figures 2A and 2B show data from experiments using lymphocytes that were separated from the lamina propria of the small intestine of SPF and sterile mice and stimulated with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, CD103, IFNγ, and GzmB were stained with antibodies and analyzed by flow cytometry. (Fig. 2A) Expression of IFNγ and CD103 (above) or GzmB (below) by gating CD8 T cells from representative mice. (Figure 2B) Summary data of the percentage of each IFNγ positive cell fraction in CD3, TCRβ and CD8 + cells. Each graph represents an individual mouse. * P <0.05 (student's t-test).

第3A圖及第3B圖展示利用淋巴細胞進行的實驗之資料，該等淋巴細胞係自由不同實驗動物設施遞送的SPF小鼠之小腸(small intestine；SI)及大腸(結腸)黏膜固有層分離且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第3A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現。(第3B圖) CD3、TCRβ及CD8+細胞內之IFNγ陽性細胞之百分比的彙總資料。每一圖表表示個別小鼠。* P ＜0.05，** P ＜0.01 (單向ANOVA)。Figures 3A and 3B show data from experiments using lymphocytes, which are small intestine (SI) and large intestine (colon) mucosal lamina propria separated from SPF mice delivered by different experimental animal facilities and Stimulation with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Figure 3A) The expression of CD8 and IFNγ by gating CD3 and TCRβ positive cells in representative mice. (Figure 3B) Summary data of the percentage of IFNγ positive cells in CD3, TCRβ and CD8 + cells. Each graph represents an individual mouse. * P <0.05, ** P <0.01 (one-way ANOVA).

第4A圖及第4B圖展示實驗之資料，其中在將來自Charles River實驗室的SPF小鼠與CLEA日本共同圈養2或6週之後，自腸(SI)及結腸黏膜固有層分離淋巴細胞且利用PMA/離子黴素刺激3.5 h。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第4A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現。(第4B圖) CD3、TCRβ及CD8+細胞內之IFNγ陽性細胞之百分比的彙總資料。每一圖表表示個別小鼠。* P ＜0.05，** P ＜0.01(單向ANOVA)。Figures 4A and 4B show experimental data in which lymphocytes were isolated from the intestine (SI) and the lamina propria of the colonic mucosa after SPF mice from the Charles River laboratory and CLEA Japan were housed in captivity for 2 or 6 weeks. Stimulation with PMA / ionomycin for 3.5 h. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Fig. 4A) The expression of CD8 and IFNγ by gating CD3 and TCRβ positive cells in representative mice. (Figure 4B) Summary data of the percentage of IFNγ positive cells in CD3, TCRβ and CD8 + cells. Each graph represents an individual mouse. * P <0.05, ** P <0.01 (one-way ANOVA).

第5A圖及第5B圖展示利用來自健康志願者之糞便進行的實驗之資料(A~F)，該等糞便係個別地在無菌乙烯基隔離器中經口投與至無菌小鼠中。四週之後，自大腸之固有層分離淋巴細胞且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第5A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現。(第5B圖) CD3、TCRβ及CD8+細胞內之IFNγ陽性細胞之百分比的彙總資料。每一圖表表示個別小鼠。** P ＜0.01 (單向ANOVA)。Figures 5A and 5B show data (A ~ F) of experiments performed using feces from healthy volunteers, which were individually administered orally to sterile mice in sterile vinyl isolators. After four weeks, lymphocytes were isolated from the lamina propria and stimulated with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Fig. 5A) Expression of CD8 and IFNγ by gating CD3 and TCRβ positive cells in representative mice. (Figure 5B) Summary data on the percentage of IFNγ positive cells in CD3, TCRβ and CD8 + cells. Each graph represents an individual mouse. ** P <0.01 (one-way ANOVA).

第6A圖及第6B圖展示利用B#5小鼠之盲腸內容物進行的實驗之資料，該內容物係經口投與至無菌小鼠。一天之後，將其飲用水換為安比西林(AMP)、甲硝噠唑(MNZ)、鏈黴素(STM)或泰黴素(Tylo.)直至實驗結束。將利用3%之氯仿治療的B#5之盲腸之內容物投與至無菌小鼠。四週之後，自大腸之固有層分離淋巴細胞且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第6A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現。(第6B圖) CD3、TCRβ及CD8+細胞內之IFNγ陽性細胞之百分比的彙總資料。每一圖表表示個別小鼠。* P ＜0.05 (單向ANOVA)。Figures 6A and 6B show data from experiments performed with the contents of the cecum of B # 5 mice, which were orally administered to sterile mice. One day later, his drinking water was changed to ampicillin (AMP), metronidazole (MNZ), streptomycin (STM) or tylosin (Tylo.) Until the end of the experiment. The contents of the cecum of B # 5 treated with 3% chloroform were administered to sterile mice. After four weeks, lymphocytes were isolated from the lamina propria and stimulated with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Fig. 6A) The expression of CD8 and IFNγ by gating CD3 and TCRβ positive cells in representative mice. (Figure 6B) Summary data of the percentage of IFNγ positive cells in CD3, TCRβ and CD8 + cells. Each graph represents an individual mouse. * P &lt; 0.05 (one-way ANOVA).

第7A圖及第7B圖展示第6A圖及第6B圖中準備的小鼠之盲腸微生物群之16S rRNA基因序列資料，該16S rRNA基因序列資料係使用下一代測序器全面地分析。(第7A圖) 操作分類單位(operational taxonomic unit；OTU)之比例之圖式。在右端，對應於B#5-AMP-2小鼠之分離菌株的OTU以綠色展示。(第7B圖) 展示分離菌株之識別及同源細菌名稱(最接近序列)以及相似性(S-ab)記分。Figures 7A and 7B show the 16S rRNA gene sequence data of the cecum microbiota of the mice prepared in Figures 6A and 6B. The 16S rRNA gene sequence data was comprehensively analyzed using a next-generation sequencer. (Figure 7A) A diagram of the ratio of the operating taxonomic unit (OTU). At the right end, the OTU corresponding to the isolated strain of B # 5-AMP-2 mice is shown in green. (Fig. 7B) The identification of the isolated strain and the homologous bacterial name (closest sequence) and similarity (S-ab) score are shown.

第8A圖及第8B圖展示關於經口投與至無菌小鼠的21種分離菌株之混合物之資料。四週之後，自大腸之固有層分離淋巴細胞且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第8A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現。(第8B圖) CD3、TCRβ及CD8+細胞內之IFNγ陽性細胞之百分比的彙總資料。每一圖表表示個別小鼠。** P ＜0.01 (學生t檢驗)。Figures 8A and 8B show information on a mixture of 21 isolated strains administered orally to sterile mice. After four weeks, lymphocytes were isolated from the lamina propria and stimulated with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Fig. 8A) The expression of CD8 and IFNγ by gated CD3 and TCRβ positive cells in representative mice. (Figure 8B) Summary data of the percentage of IFNγ positive cells in CD3, TCRβ and CD8 + cells. Each graph represents an individual mouse. ** P <0.01 (student's t-test).

第9A圖及第9B圖展示關於經口投與至無菌小鼠的21種分離菌株之混合物之資料。四週之後，自大腸之固有層分離淋巴細胞且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8、CD103、IFNγ及GzmB且藉由流動式細胞測量術分析。(第9A圖) 藉由代表性小鼠之閘控CD8 T細胞進行的IFNγ及CD103 (上列)或GzmB (下列)之表現。(第9B圖) CD3、TCRβ及CD8+細胞內之每一IFNγ陽性細胞餾分之百分比的彙總資料。每一圖表表示個別小鼠。* P ＜0.05，** P ＜0.01 (學生t檢驗)。Figures 9A and 9B show information on a mixture of 21 isolated strains administered orally to sterile mice. After four weeks, lymphocytes were isolated from the lamina propria and stimulated with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, CD103, IFNγ, and GzmB were stained with antibodies and analyzed by flow cytometry. (Fig. 9A) Expression of IFNγ and CD103 (above) or GzmB (below) by gated CD8 T cells of representative mice. (Figure 9B) Summary data of the percentage of each IFNγ positive cell fraction in CD3, TCRβ and CD8 + cells. Each graph represents an individual mouse. * P <0.05, ** P <0.01 (student's t-test).

第10A圖及第10B圖展示關於經口投與至無菌小鼠的21種菌株或11種菌株(相應於菌株#1-11之菌株混合物；參見表1)之混合物之資料。四週之後，自大腸之固有層分離淋巴細胞且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第10A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現。(第10B圖) CD3、TCRβ及CD8+細胞內之IFNγ陽性細胞之百分比的彙總資料。每一圖表表示個別小鼠。*** P ＜0.001，****P ＜0.0001 (單向ANOVA)。Figures 10A and 10B show information on a mixture of 21 strains or 11 strains (corresponding to strain mixtures of strains # 1-11; see Table 1) administered orally to sterile mice. After four weeks, lymphocytes were isolated from the lamina propria and stimulated with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Fig. 10A) Expression of CD8 and IFNγ by gating CD3 and TCRβ positive cells in representative mice. (Figure 10B) Summary data of the percentage of IFNγ positive cells in CD3, TCRβ and CD8 + cells. Each graph represents an individual mouse. *** P <0.001, **** P <0.0001 (one-way ANOVA).

第11圖展示接種至GF小鼠中的10-混合細菌菌株及11-混合細菌菌株之組成物(參見第12A圖及第12B圖)。Figure 11 shows the composition of 10-mixed bacterial strains and 11-mixed bacterial strains inoculated into GF mice (see Figures 12A and 12B).

第12A圖及第12B圖展示自11或10種菌株之混合物(參見第11圖)，或為已知Treg誘導物之17種菌株之混合物獲得的資料，該等菌株係經口投與至無菌小鼠。四週之後，自大腸之固有層分離淋巴細胞且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第12A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現。(第12B圖) CD3+ TCRb+細胞中之CD8+ IFNγ+細胞(左)、CD8T細胞中之IFNγ+細胞(中)之百分比及CD8+ IFNγ+細胞之數量(右)的彙總資料。每一圖表表示個別小鼠。** P ＜0.01，*** P ＜0.001，****P ＜0.0001(單向ANOVA)。Figures 12A and 12B show data obtained from a mixture of 11 or 10 strains (see Figure 11), or a mixture of 17 strains of known Treg inducers, which were administered orally to sterile Mice. After four weeks, lymphocytes were isolated from the lamina propria and stimulated with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Fig. 12A) The expression of CD8 and IFNγ by gating CD3 and TCRβ positive cells in representative mice. (Figure 12B) Summary data of CD8 + IFNγ + cells in CD3 + TCRb + cells (left), percentage of IFNγ + cells in CD8T cells (middle), and number of CD8 + IFNγ + cells (right). Each graph represents an individual mouse. ** P <0.01, *** P <0.001, **** P <0.0001 (one-way ANOVA).

第13圖展示系統樹，該系統樹係由11種菌株之16S rRNA基因序列(參見第11圖)、其最接近序列及一些類型菌株使用MEGA v5.0套件及相鄰-接合方法來構造。亦展示作為7混合或4混合接種至GF小鼠中的菌株(接種實驗之結果係展示於第14A圖及第14B圖)。Figure 13 shows a phylogenetic tree constructed from the 16S rRNA gene sequence of 11 strains (see Figure 11), its closest sequence, and some types of strains using the MEGA v5.0 kit and the adjacent-joining method. Strains inoculated into GF mice as 7 or 4 mixes are also shown (the results of the inoculation experiments are shown in Figures 14A and 14B).

第14A圖及第14B圖展示經口投與至無菌小鼠的11種菌株之混合物、第13圖列出的7菌株混合物或4菌株混合物之資料。四週之後，自大腸之固有層分離淋巴細胞且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第14A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現。(第14B圖) CD3+ TCRb+細胞中之CD8+ IFNγ+細胞(左)、CD8T細胞中之IFNγ+細胞(中)之百分比及CD8+ IFNγ+細胞之數量(右)的彙總資料。每一圖表表示個別小鼠。P ＜0.05，** P ＜0.01，*** P ＜0.001(單向ANOVA)。Figures 14A and 14B show information on a mixture of 11 strains orally administered to sterile mice, a mixture of 7 strains, or a mixture of 4 strains listed in Figure 13. After four weeks, lymphocytes were isolated from the lamina propria and stimulated with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Fig. 14A) Expression of CD8 and IFNγ by gating CD3 and TCRβ positive cells in representative mice. (Figure 14B) Summary data of CD8 + IFNγ + cells in CD3 + TCRb + cells (left), percentage of IFNγ + cells in CD8T cells (middle), and number of CD8 + IFNγ + cells (right). Each graph represents an individual mouse. P <0.05, ** P <0.01, *** P <0.001 (one-way ANOVA).

第15圖展示利用六週大SPF C57BL/6小鼠進行的實驗之資料，該小鼠係自日本SLC購買且在其飲用水中利用抗生素(1 g/L安比西林、0.5 g/L萬古黴素、1 g/L甲硝噠唑及1 g/L新黴素；「AVMN」)來治療。隨後，在第0天，利用3x105 MC38腫瘤細胞系皮下注射小鼠於右側腹中。當腫瘤出現且可觸知時，停止抗生素治療(第2天)。在第3天、第5天及第9天利用200 μg之抗PD1抗體(純系J43)腹膜內注射小鼠(「+抗PD1Ab」)。一週2或3次(包括第3天、第5天及第9天)用11混合胃管灌食小鼠(「+11混合」)。使用測徑規量測腫瘤大小且腫瘤體積係測定為長度x寬度2 x 0.5。** P ＜0.01，*** P ＜0.001，**** P ＜0.0001 (雙向ANOVA)。Figure 15 shows data from experiments performed with six-week-old SPF C57BL / 6 mice purchased from SLC Japan and using antibiotics (1 g / L ampicillin, 0.5 g / L vancomycete) in their drinking water. 1 mg / L metronidazole and 1 g / L neomycin; "AVMN"). Subsequently, on day 0, mice were injected subcutaneously into the right abdomen using a 3x10 5 MC38 tumor cell line. When the tumor appeared and was palpable, antibiotic therapy was discontinued (day 2). Mice were injected intraperitoneally on day 3, day 5 and day 9 with 200 μg of anti-PD1 antibody (pure line J43) ("+ anti-PD1Ab"). Mice were fed with 11 mixed gastric tubes 2 or 3 times a week (including days 3, 5, and 9) ("+11 mixed"). Tumor size was measured using a caliper and tumor volume was measured as length x width 2 x 0.5. ** P <0.01, *** P <0.001, **** P <0.0001 (two-way ANOVA).

第16A圖及第16B圖展示關於自腫瘤細胞分離的淋巴細胞之資料。在第23天或第27天，自腫瘤分離淋巴細胞且用PMA/離子黴素刺激4小時。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第16A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現。(第16B圖) CD3+ TCRb+細胞中之CD8+ IFNγ+細胞(左)、CD8T細胞中之IFNγ+細胞(中)之百分比及CD8+ IFNγ+細胞之數量(右)的彙總資料。每一圖表表示個別小鼠。* P ＜0.05，** P ＜0.01，*** P ＜0.001 (單向ANOVA)。Figures 16A and 16B show information on lymphocytes isolated from tumor cells. On days 23 or 27, lymphocytes were isolated from the tumor and stimulated with PMA / ionomycin for 4 hours. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Fig. 16A) Expression of CD8 and IFNγ by gating CD3 and TCRβ positive cells in representative mice. (Figure 16B) Summary data of CD8 + IFNγ + cells in CD3 + TCRb + cells (left), percentage of IFNγ + cells in CD8T cells (middle), and number of CD8 + IFNγ + cells (right). Each graph represents an individual mouse. * P <0.05, ** P <0.01, *** P <0.001 (one-way ANOVA).

第17A圖、第17B圖及第18圖展示關於自腫瘤細胞分離的淋巴細胞之資料。在第23天或第27天，自腫瘤分離淋巴細胞且用PMA/離子黴素刺激4小時。利用抗體及肽-H2Kb 四聚物染色CD3、TCRβ、CD8、gp70 MC38肽(KSPWFTTL(SEQ ID NO:53))特異性TCR、CD44、GzmB及IFNγ，且藉由流動式細胞測量術分析。(第17A圖) 藉由代表性小鼠之閘控CD3、TCRβ及CD8+細胞進行的gp70特異性TCR、CD44、GzmB及IFNγ之表現。(第17B圖)。CD8T細胞內之每一IFNγ陽性細胞餾分之百分比的彙總資料。每一圖表表示個別小鼠。** P ＜0.01，*** P ＜0.001，**** P ＜0.0001 (單向ANOVA)。對IFNγ+CD4 T細胞之效應展示於第18圖中。Figures 17A, 17B and 18 show information on lymphocytes isolated from tumor cells. On days 23 or 27, lymphocytes were isolated from the tumor and stimulated with PMA / ionomycin for 4 hours. CD3, TCRβ, CD8, gp70 MC38 peptide (KSPWFTTL (SEQ ID NO: 53)) specific TCR, CD44, GzmB and IFNγ were stained with antibodies and peptide-H2K b tetramer, and analyzed by flow cytometry. (Figure 17A) Expression of gp70-specific TCR, CD44, GzmB, and IFNγ by gating CD3, TCRβ, and CD8 + cells from representative mice. (Figure 17B). Summary data for the percentage of each IFNγ positive cell fraction in CD8T cells. Each graph represents an individual mouse. ** P <0.01, *** P <0.001, **** P <0.0001 (one-way ANOVA). The effect on IFNγ + CD4 T cells is shown in Figure 18.

第19圖展示關於自腫瘤細胞分離的淋巴細胞之資料。在第23天或第27天，分離完整脾細胞且以每孔106 個細胞塗覆且在37℃下利用0.5 μg/mL gp70 MC38肽(KSPWFTTL (SEQ ID NO:53))刺激36小時。使用小鼠IFNγELISPOT Ready-SET Go!® 套組(eBioscience)生成斑點，且使用Immunospot 4系分析器量測斑點之數量且使用ImmunoSpot軟體(Cellular Technology)分析。每一圖表表示個別小鼠。「原始」為未利用抗生素治療，未利用MC38細胞注射且未利用11混合及抗PD1抗體治療的小鼠。* P ＜0.05，** P ＜0.01，*** P ＜0.001 (單向ANOVA)。Figure 19 shows information on lymphocytes isolated from tumor cells. Day 23 or day 27, splenocytes isolated and complete at 106 cells per well and coated using 0.5 μg / mL gp70 MC38 peptide (KSPWFTTL (SEQ ID NO: 53 )) at 37 [deg.] C stimulated for 36 hours. The spots were generated using a mouse IFNγELISPOT Ready-SET Go! ® kit (eBioscience), and the number of spots was measured using an Immunospot 4 series analyzer and analyzed using ImmunoSpot software (Cellular Technology). Each graph represents an individual mouse. "Original" are mice that were not treated with antibiotics, were not injected with MC38 cells, and were not treated with 11 mixed and anti-PD1 antibodies. * P <0.05, ** P <0.01, *** P <0.001 (one-way ANOVA).

第20圖展示關於包括11種選定菌株的26種分離菌株之資料。Figure 20 shows information on 26 isolated strains including 11 selected strains.

第21圖展示關於藉由11混合細菌菌株誘導GzmB+ IFNγ+CD8 T細胞之資料。Figure 21 shows data on the induction of GzmB + IFNγ + CD8 T cells by 11 mixed bacterial strains.

第22圖展示較慢腫瘤生長伴隨有IFNγ+CD8 T細胞至腫瘤中之增加浸潤。Figure 22 shows that slower tumor growth is accompanied by increased infiltration of IFNγ + CD8 T cells into the tumor.

第23圖展示αPD1 Ab及11混合細菌菌株之組合加強GzmB+ IFNγ+CD8細胞毒細胞至腫瘤中之浸潤。Figure 23 shows that the combination of αPD1 Ab and 11 mixed bacterial strains enhances the infiltration of GzmB + IFNγ + CD8 cytotoxic cells into tumors.

第24圖展示關於利用11混合及/或抗CTLA-4抗體進行之治療的實例4中描述的實驗計畫之示意圖。Figure 24 shows a schematic diagram of the experimental scheme described in Example 4 regarding treatment with 11 mixed and / or anti-CTLA-4 antibodies.

第25圖展示接收αCTLA-4 Ab及細菌菌株之11混合之組合的小鼠之體重(左圖面)。接收αCTLA-4 Ab及細菌菌株之11混合之組合的小鼠在第24圖呈現的實驗(實例4)中具有顯著的腫瘤生長減少(右圖面)。Figure 25 shows the weight of mice receiving a combination of αCTLA-4 Ab and 11 strains of bacterial strains (left panel). Mice receiving a combination of αCTLA-4 Ab and 11 strains of bacterial strains had a significant reduction in tumor growth in the experiment presented in Figure 24 (Example 4) (right panel).

第26圖展示αCTLA-4 Ab及細菌菌株之11混合之組合在第23圖中呈現的實驗(實例4)中對小鼠之存活具有顯著效應。Figure 26 shows that the combination of αCTLA-4 Ab and 11 strains of bacterial strains had a significant effect on mouse survival in the experiment presented in Figure 23 (Example 4).

第27圖展示在實例4中描述的實驗中所治療的個別小鼠之腫瘤體積圖表(對照，11混合；αCTLA-4 Ab；11混合+ αCTLA-4 Ab)。Figure 27 shows a tumor volume chart for individual mice treated in the experiment described in Example 4 (control, 11 mixed; αCTLA-4 Ab; 11 mixed + αCTLA-4 Ab).

第28圖展示關於利用11混合或4混合及/或抗PD-1抗體進行之治療的實例5中描述的實驗計畫之示意圖。FIG. 28 shows a schematic diagram of the experimental scheme described in Example 5 regarding treatment with 11 or 4 mixed and / or anti-PD-1 antibodies.

第29圖展示接收αPD1 Ab及細菌菌株之4混合或αPD1 Ab及細菌菌株之11混合之組合，及各種對照組的小鼠之體重(左圖面)及腫瘤體積(右圖面)。Figure 29 shows the body weight (left panel) and tumor volume (right panel) of mice receiving various combinations of αPD1 Ab and bacterial strain 4 mix or αPD1 Ab and bacterial strain 11 mix.

第30圖展示在實例5之實驗中所治療的個別小鼠之腫瘤體積圖表(11混合；αPD-1 Ab；11混合+ αPD-1 Ab)。在11混合+ αPD-1 Ab治療組(底部右圖面)中，在多個動物中腫瘤體積不增加。Figure 30 shows a tumor volume chart of individual mice treated in the experiment of Example 5 (11 mixed; αPD-1 Ab; 11 mixed + αPD-1 Ab). In the 11 mixed + αPD-1 Ab treatment group (bottom right panel), tumor volume did not increase in multiple animals.

第31圖展示在實例5之實驗中所治療的小鼠之存活圖表(11混合；αPD-1 Ab；11混合+ αPD-1 Ab)。Figure 31 shows the survival charts of mice treated in the experiment of Example 5 (11 mixed; αPD-1 Ab; 11 mixed + αPD-1 Ab).

第32圖展示在實例5之實驗中所治療的個別小鼠之腫瘤體積圖表(4混合；αPD-1 Ab；4混合+ αPD-1 Ab)。在4混合+ αPD-1 Ab治療組(底部右圖面)中，在多個動物中腫瘤體積不增加。Figure 32 shows a tumor volume chart of individual mice treated in the experiment of Example 5 (4 mixed; αPD-1 Ab; 4 mixed + αPD-1 Ab). In the 4 mixed + αPD-1 Ab treatment group (bottom right panel), tumor volume did not increase in multiple animals.

第33圖展示在實例5之實驗中治療的小鼠之圖表。突顯的為利用αPD-1 Ab、11混合+ αPD-1 Ab及4混合+ αPD-1 Ab進行的治療。Figure 33 shows a graph of mice treated in the experiment of Example 5. Highlighting are the treatments using αPD-1 Ab, 11 mixed + αPD-1 Ab, and 4 mixed + αPD-1 Ab.

第34圖展示利用Braf Pten黑素瘤模型進行之實驗(實例6)之資料。簡言之，自第-3天至第2天投與小鼠抗生素(「AVMN」)，且在第0天利用7x105 Braf Pten細胞植入。在第3天、第6天及第9天，在利用或不利用11混合(時間線上帶星號之箭頭)的情況下，對所指示小鼠組投與抗PD1抗體(時間線上之箭頭)及自日本SLC獲得的無特定病原(specific-pathogen free；SPF)小鼠之SLC SPF糞便(SLC SPF糞便)。指示為已接收11混合之小鼠組每週投與11混合2或3次。圖表展示在每一時間點針對小鼠組之平均腫瘤體積，**** P＜0.0001，*** P＜0.001 (雙向ANOVA)。Figure 34 shows data from an experiment (Example 6) using the Braf Pten melanoma model. Briefly, mice were administered antibiotics ("AVMN") from day -3 to day 2 and implanted with 7x10 5 Braf Pten cells on day 0. On the 3rd, 6th, and 9th days, anti-PD1 antibody (arrows on the timeline) was administered to the indicated mouse groups with or without the use of the 11 mixture (arrows with timelines on the timeline) and SLC SPF feces (SLC SPF feces) from specific-pathogen free (SPF) mice obtained from SLC in Japan. Groups of mice that have received 11 mixes are given 11 mixes 2 or 3 times per week. The graph shows the average tumor volume for the mouse group at each time point, **** P <0.0001, *** P <0.001 (two-way ANOVA).

第35圖展示利用Braf Pten黑素瘤模型進行之實驗(實例6)之資料。簡言之，自第-3天至第2天投與小鼠抗生素(「AVMN」)，且在第0天利用7x105 Braf Pten細胞植入。在第3天、第6天及第9天，在利用或不利用11混合(時間線上帶星號之箭頭)的情況下，對所指示小鼠組投與抗PD1抗體(時間線上之箭頭)及自日本SLC獲得的無特定病原(specific-pathogen free；SPF)小鼠之SLC SPF糞便(SLC SPF糞便)。指示為已接收11混合之小鼠組每週投與11混合2或3次。圖表展示在每一時間點針對小鼠組之平均腫瘤面積。**** P＜0.0001，*** P＜0.001 (雙向ANOVA)。Figure 35 shows data from an experiment (Example 6) using the Braf Pten melanoma model. Briefly, mice were administered antibiotics ("AVMN") from day -3 to day 2 and implanted with 7x10 5 Braf Pten cells on day 0. On the 3rd, 6th, and 9th days, anti-PD1 antibody (arrows on the timeline) was administered to the indicated mouse groups with or without the use of the 11 mixture (arrows with an asterisk on the timeline) and SLC SPF feces (SLC SPF feces) from specific-pathogen free (SPF) mice obtained from SLC in Japan. Groups of mice that have received 11 mixes are given 11 mixes 2 or 3 times per week. The graph shows the average tumor area for the mouse group at each time point. **** P <0.0001, *** P <0.001 (two-way ANOVA).

第36圖展示關於在第22天及第24天自所指示小鼠組獲得的腫瘤之重量之資料。* P＜0.05 (單向ANOVA)。Figure 36 shows data on tumor weights obtained from the indicated mouse groups on days 22 and 24. * P <0.05 (one-way ANOVA).

第37A圖-第37C圖展示關於自腫瘤細胞分離的淋巴細胞之資料。在第22天及第24天，自腫瘤分離淋巴細胞。利用抗體染色CD3、TCRβ、CD8及IFNγ。第37A圖展示自腫瘤分離的細胞之CD3+ TCRβ+CD8α+群體中之CD8+ IFNγ+細胞的百分比。第37B圖展示自腫瘤分離的CD8+ IFNγ+細胞之數量。第37C圖展示每公克腫瘤的CD8+ IFNγ+細胞數量。** P＜0.01，* P＜0.05 (單向ANOVA)。Figures 37A-37C show information on lymphocytes isolated from tumor cells. Lymphocytes were isolated from tumors on days 22 and 24. CD3, TCRβ, CD8 and IFNγ were stained with antibodies. Figure 37A shows the percentage of CD8 + IFNγ + cells in the CD3 + TCRβ + CD8α + population of cells isolated from tumors. Figure 37B shows the number of CD8 + IFNγ + cells isolated from the tumor. Figure 37C shows the number of CD8 + IFNγ + cells per gram of tumor. ** P <0.01, * P <0.05 (one-way ANOVA).

第38圖展示自腫瘤分離的CD8T細胞之群體中之IFNγ+細胞的百分比。*** P＜0.001，** P＜0.01，* P＜0.05 (單向ANOVA)。Figure 38 shows the percentage of IFNγ + cells in a population of CD8 T cells isolated from tumors. *** P <0.001, ** P <0.01, * P <0.05 (one-way ANOVA).

第39A圖-第39D圖展示關於自腫瘤細胞分離的淋巴細胞之資料。在第22天及第24天，自腫瘤分離淋巴細胞。利用抗體染色CD3、TCRβ、CD8、IFNγ、GzmB、IL-17及CD4。第39A圖展示自腫瘤分離的細胞之CD3+ TCRβ+CD8α+群體中之IFNγ+ GzmB+細胞的百分比。第39B圖展示自腫瘤分離的細胞之CD3+ TCRβ+ CD4+群體中之Th1細胞的百分比。第39C圖展示自腫瘤分離的細胞之CD3+ TCRβ+ CD4+群體中之Th17細胞的百分比。第39D圖展示自腫瘤分離的細胞之CD3+ TCRβ+ CD4+群體中之Treg細胞的百分比。Figures 39A-39D show information on lymphocytes isolated from tumor cells. Lymphocytes were isolated from tumors on days 22 and 24. CD3, TCRβ, CD8, IFNγ, GzmB, IL-17 and CD4 were stained with antibodies. Figure 39A shows the percentage of IFNγ + GzmB + cells in the CD3 + TCRβ + CD8α + population of cells isolated from tumors. Figure 39B shows the percentage of Th1 cells in the CD3 + TCRβ + CD4 + population of cells isolated from tumors. Figure 39C shows the percentage of Th17 cells in the CD3 + TCRβ + CD4 + population of cells isolated from tumors. Figure 39D shows the percentage of Treg cells in the CD3 + TCRβ + CD4 + population of cells isolated from tumors.

第40圖展示實例7中描述的實驗計畫(給藥研究)之示意圖。Figure 40 shows a schematic diagram of the experimental plan (dose study) described in Example 7.

第41A圖-第41C圖展示關於在第40圖展示的實驗(實例7)中自小鼠分離的淋巴細胞之資料。利用抗體染色CD3、TCRβ、CD8及IFNγ。第41A圖展示自所指示小鼠分離的細胞之CD3+ TCRβ+ CD8α+群體中之CD8+ IFNγ+細胞的百分比。第41B圖展示自所指示小鼠分離的CD8+ IFNγ+細胞之數量。第41C圖展示自所指示小鼠分離的CD8T細胞之群體中之IFNγ+細胞的百分比。Figures 41A-41C show information on lymphocytes isolated from mice in the experiment shown in Figure 40 (Example 7). CD3, TCRβ, CD8 and IFNγ were stained with antibodies. Figure 41A shows the percentage of CD8 + IFNγ + cells in the CD3 + TCRβ + CD8α + population of cells isolated from the indicated mice. Figure 41B shows the number of CD8 + IFNγ + cells isolated from the indicated mice. Figure 41C shows the percentage of IFNγ + cells in the population of CD8 T cells isolated from the indicated mice.

第42A圖-第42C圖展示關於自第40圖展示的實驗(實例7)之小鼠分離的淋巴細胞之資料。利用抗體染色CD3、TCRβ、CD8、IFNγ、CD103、IL-17及CD4。第42A圖展示自所指示小鼠分離的細胞之CD3+ TCRβ+ CD8α+群體中之IFNγ+ CD103+細胞的百分比。第42B圖展示自所指示小鼠分離的細胞之CD3+ TCRβ+ CD4+群體中之Th17細胞的百分比。第42C圖展示自所指示小鼠分離的細胞之CD3+ TCRβ+ CD4+群體中之Th1細胞的百分比。Figures 42A-42C show information on lymphocytes isolated from the mice of the experiment shown in Figure 40 (Example 7). CD3, TCRβ, CD8, IFNγ, CD103, IL-17 and CD4 were stained with antibodies. Figure 42A shows the percentage of IFNγ + CD103 + cells in the CD3 + TCRβ + CD8α + population of cells isolated from the indicated mice. Figure 42B shows the percentage of Th17 cells in the CD3 + TCRβ + CD4 + population of cells isolated from the indicated mice. Figure 42C shows the percentage of Th1 cells in the CD3 + TCRβ + CD4 + population of cells isolated from the indicated mice.

第43A圖-第43C圖及第44圖展示來自實例8之實驗的結果。實驗展示11混合需要BATF3來誘導CD8-T細胞。不需要BATF3來誘導Th17。第43A圖展示自所指示小鼠分離的細胞之CD3+ TCRβ+ CD8α+ (CD8 T細胞)群體中之IFNγ+的百分比。第43B圖展示CD8+ IFNγ+細胞之數量。第43C圖展示自所指示小鼠分離的細胞之CD3+ TCRβ+ CD4+群體中之Th17細胞的百分比。**** P＜0.0001，*** P＜0.001，** P＜0.01，* P＜0.05 (單向ANOVA)。第44圖展示11混合需要BATF3來誘導CD8-T細胞，如藉由流動式細胞測量術所證明(第44A圖)，且展示自所指示小鼠分離的細胞之CD3+ TCRβ+ CD8α+ (CD8 T細胞)群體中之IFNγ+的百分比(第44B圖)。Figures 43A-43C and 44 show the results of the experiment from Example 8. The experiments showed that the 11 mix required BATF3 to induce CD8-T cells. BATF3 is not required to induce Th17. Figure 43A shows the percentage of IFNγ + in the CD3 + TCRβ + CD8α + (CD8 T cell) population of cells isolated from the indicated mice. Figure 43B shows the number of CD8 + IFNγ + cells. Figure 43C shows the percentage of Th17 cells in the CD3 + TCRβ + CD4 + population of cells isolated from the indicated mice. **** P <0.0001, *** P <0.001, ** P <0.01, * P <0.05 (one-way ANOVA). Figure 44 shows that 11 mixes require BATF3 to induce CD8-T cells, as demonstrated by flow cytometry (Figure 44A), and show CD3 + TCRβ + CD8α + (CD8 T Cells) The percentage of IFNγ + in the population (Figure 44B).

第45圖-第46圖展示來自實例9之實驗的結果。實驗展示11混合在治療李氏菌屬(Listeria)感染方面為有效的。第45圖展示糞便+11混合在清除來自受感染小鼠之李氏菌屬方面為有效的，如以糞便中李氏菌屬CFU之量的減少所證明。第46圖展示利用糞便及11混合治療的李氏菌感染小鼠之體重高於僅利用糞便進行的治療。Figures 45-46 show the results from the experiment of Example 9. Experiments have shown that the 11 mix is effective in treating Listeria infections. Figure 45 shows that feces + 11 mix is effective in removing Listeria from infected mice, as evidenced by a reduction in the amount of Listeria CFU in the stool. Figure 46 shows that the weight of Listeria-infected mice treated with feces and 11 was higher than that treated with feces alone.

第47A圖及第47B圖展示關於實例2之資料。11種菌株之混合物、第13圖中列出的7種菌株混合物或4種菌株混合物經口投與至無菌小鼠。四週之後，自大腸之固有層分離淋巴細胞且利用PMA/離子黴素刺激3.5小時。利用抗體染色CD3、TCRβ、CD8及IFNγ且藉由流動式細胞測量術分析。(第47A圖) 藉由代表性小鼠之閘控CD3及TCRβ陽性細胞進行的CD8及IFNγ之表現展示在第47B圖，如藉由CD8T細胞中之IFNγ+細胞之百分比所指示。每一圖表表示個別小鼠。* P ＜0.05，** P ＜0.01，*** P ＜0.001 (單向ANOVA)。Figures 47A and 47B show information about Example 2. A mixture of 11 strains, a mixture of 7 strains listed in Figure 13 or a mixture of 4 strains was orally administered to sterile mice. After four weeks, lymphocytes were isolated from the lamina propria and stimulated with PMA / ionomycin for 3.5 hours. CD3, TCRβ, CD8, and IFNγ were stained with antibodies and analyzed by flow cytometry. (Figure 47A) The performance of CD8 and IFNγ by gated CD3 and TCRβ positive cells from representative mice is shown in Figure 47B, as indicated by the percentage of IFNγ + cells in CD8T cells. Each graph represents an individual mouse. * P <0.05, ** P <0.01, *** P <0.001 (one-way ANOVA).

第48圖係關於實例10且展示11混合在小鼠中之CD8誘導效應(在其他情況下未面臨挑戰)限於腸/腸道隔室。(SI = 短腸，CIEL =結腸上皮內淋巴細胞，LN = 淋巴結)Figure 48 is about Example 10 and shows that the CD8-inducing effect of 11 mixed in mice (which otherwise did not face challenges) is limited to the intestinal / intestinal compartment. (SI = short intestine, CIEL = colon intraepithelial lymphocytes, LN = lymph nodes)

第49圖展示結腸LP中DC子集之頻率僅藉由利用11混合之菌落形成輕微地改變。Figure 49 shows that the frequency of the DC subset in the colonic LP was only slightly changed by using colony formation of the 11 mix.

第50圖-第52圖展示MHC CLP類別細胞係藉由11混合之投與活化，且該活化在活化之第一週內最強。不存在MHC MLN類別細胞之活化。第50圖及第51圖中展示個別量測，而第52圖中描繪累積的資料。Figures 50-52 show that the MHC CLP class cell line was activated by the administration of 11 mix, and the activation was strongest in the first week of activation. There is no activation of MHC MLN class cells. Individual measurements are shown in Figures 50 and 51, while accumulated data are depicted in Figure 52.

第53圖及第54圖展示MHC CLP類別細胞係藉由11混合之投與活化，而不存在MHC MLN類別細胞之活化。個別量測展示在第53圖中，而累積的資料描繪在第54圖中，其表示為CD3+ TCDRβ+ CD8a+細胞之百分比。Figures 53 and 54 show that MHC CLP-type cell lines are activated by the administration of a mixture of 11 without activation of MHC MLN-type cells. Individual measurements are shown in Figure 53 and the accumulated data is depicted in Figure 54 as a percentage of CD3 + TCDRβ + CD8a + cells.

第55圖展示MHC CLP類別細胞係藉由11混合之投與活化，如藉由Ki67狀態所證明，而不存在MHC MLN類別細胞之活化。Figure 55 shows that MHC CLP-type cell lines are activated by the administration of 11 mixes, as demonstrated by Ki67 status, and there is no activation of MHC MLN-type cells.

第56圖及第57圖展示MHC CLP類別細胞係藉由11混合之投與活化，如藉由CD103+狀態所證明，而不存在MHC MLN類別細胞之活化。個別量測展示在第56圖中，而累積的資料描繪在第57圖中，其表示為CD3+ TCRβ+ CD8a+ IFNγ+細胞之百分比。Figures 56 and 57 show that MHC CLP-type cell lines are activated by a mixed administration of 11, as evidenced by the CD103 + status, and there is no activation of MHC MLN-type cells. Individual measurements are shown in Figure 56 and the accumulated data is depicted in Figure 57, which is expressed as the percentage of CD3 + TCRβ + CD8a + IFNγ + cells.

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Claims (226)

一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。A composition comprising a purified bacterial mixture, the purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcerans, Bacteroides doelis, Bacteroides uniformis, Rare Micrococcus, Paraprevotella xylaniphila, Paramycobacterium yojei, Albibacterium, Paramycobacterium gordonii, Eumycobacterium myxobacteria, Paramycobacterium dirichli, Bacillus cellulolyticus, Bacillus clacherii, Fecal anaerobic stick Bacteria, Bacteroides fragrans, Bacteroides fragile, Bacteroides morphogenes, Bacteroides escherichia, Clostridium, Pseudomonas archaea, Bacteroides, Trichomonas bacteria HGA0140, Hungatella hathewayi, Lavasio Bacteria, rumen coccus and harmless clostridium. 如請求項1所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。The composition according to claim 1, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten At least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, At least 23, at least 24, at least 25, or at least 26 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。A composition comprising a purified bacterial mixture, the purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcerans, Bacteroides doelis, Bacteroides uniformis, Rare Micrococcus, Paraprevotella xylaniphila, Paramycobacterium yojei, Albibacterium, Paramycobacterium gordonii, Eumycobacterium myxobacteria, Paramycobacterium dirichli, Bacillus cellulolyticus, Bacillus clacherii, Fecal anaerobic stick Fungi, Bacteroides selenoides, Bacteroides fragile, Bacteroides morphogenes, Bacteroides escherichia, Clostridium, P. archaea and Bacteroides. 如請求項3所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。The composition according to claim 3, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、多利擬桿菌、單形擬桿菌、罕見小球菌屬、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。A composition comprising a purified bacterial mixture, the purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcerans, Bacteroides doelis, Bacteroides uniformis Rare Micrococcus, Paraprevotella xylaniphila, Parabacillus yojei, Allobacterium, Paragliobacterium gordonii, Eumycobacterium myxobacteria, and Paracoccus diidii. 如請求項5所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。The composition according to claim 5, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species or at least 11 strains of bacteria. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。A composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: B. cellulolyticus, B. clarkii, anaerobic corynebacterium Bacteroides selenoides, Bacteroides fragile, Bacteroides escherichia, Clostridium, B. archaebacterium, Bacteroides, Trichophytons HGA0140, Hungatella hathewayi, Clostridium lavas, Rumen Cocci and harmless Clostridium. 如請求項7所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。The composition according to claim 7, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。A composition comprising a purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: B. cellulolyticus, B. clarkii, anaerobic coryneform bacteria, Bacteroides selenoides, B. fragile, B. monomorphe, B. escherichia, Clostridium, B. parvii and Bacteroides. 如請求項9所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。The composition according to claim 9, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten A bacterial strain. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、潰瘍梭桿菌、罕見小球菌屬及黏液真桿菌。A composition comprising a purified bacterial mixture, the purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium ulcer, Rare micrococcus, and Eumycobacterium myxoidum. 如請求項11所述之組成物，其中該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。The composition according to claim 11, wherein the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：多利擬桿菌、單形擬桿菌、Paraprevotella xylaniphila、約氏副擬桿菌、別樣桿菌屬、戈登副擬桿菌及狄氏副擬桿菌。A composition comprising a purified bacterial mixture, the purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Bacteroides dorsii, Bacteroides monomorphe, Paraprevotella xylaniphila, Bacteroides yojei, Allobacterium, Paragliobacterium gordonii, and Paracoccus difficile. 如請求項13所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。The composition according to claim 13, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to the following: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10.SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. 如請求項15所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。The composition according to claim 15, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten At least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, At least 23, at least 24, at least 25, or at least 26 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to the following: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10.SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, or SEQ ID NO: 21. 如請求項17所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。The composition according to claim 17, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to the following: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11. 如請求項19所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。The composition according to claim 19, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species or at least 11 strains of bacteria. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the following: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21. SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 26. 如請求項21所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。The composition according to claim 21, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20或SEQ ID NO:21。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the following: SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: twenty one. 如請求項23所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。The composition according to claim 23, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten A bacterial strain. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:5或SEQ ID NO:10。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to the following: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5 or SEQ ID NO: 10. 如請求項25所述之組成物，其中該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。The composition of claim 25, wherein the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:11。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology to the following: SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. 如請求項27所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。The composition of claim 27, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the following: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36.SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. 如請求項29所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。The composition according to claim 29, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten At least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, At least 23, at least 24, at least 25, or at least 26 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46及SEQ ID NO:47。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the following: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36.SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, and SEQ ID NO: 47. 如請求項31所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。The composition according to claim 31, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36或SEQ ID NO:37。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the following: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36 or SEQ ID NO: 37. 如請求項33所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。The composition according to claim 33, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species or at least 11 strains of bacteria. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51或SEQ ID NO:52。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the following: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47. SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 or SEQ ID NO: 52. 如請求項35所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種或至少15種細菌菌株。The composition according to claim 35, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species, at least 11, at least 12, at least 13, at least 14, or at least 15 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46或SEQ ID NO:47。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the following: SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46 or SEQ ID NO: 47. 如請求項37所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。The composition of claim 37, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten A bacterial strain. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:31或SEQ ID NO:36。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the following: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 31 or SEQ ID NO: 36. 如請求項39所述之組成物，其中該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。The composition of claim 39, wherein the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下各項具有至少95%同源性之16S rDNA序列：SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35或SEQ ID NO:37。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the following: SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 37. 如請求項41所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。The composition according to claim 41, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains. 如前述請求項中任一項所述之組成物，其中該一或多個細菌菌株包含與該等SEQ ID NO具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。The composition of any one of the preceding claims, wherein the one or more bacterial strains comprise 16S having at least 96%, at least 97%, at least 98%, or at least 99% homology with the SEQ ID NOs rDNA sequence. 如前述請求項中任一項所述之組成物，其中該等細菌菌株之至少50%屬於擬桿菌目。The composition according to any one of the preceding claims, wherein at least 50% of the bacterial strains belong to the order Bacteroides. 如前述請求項中任一項所述之組成物，其中該等細菌菌株中之一或多者屬於擬桿菌目，且該等細菌菌株中之一或多者屬於梭菌目。The composition according to any one of the preceding claims, wherein one or more of the bacterial strains belong to the order Bacteroides, and one or more of the bacterial strains belong to the order Clostridia. 如前述請求項中任一項所述之組成物，其中該等細菌菌株之至少25%屬於擬桿菌科。The composition according to any one of the preceding claims, wherein at least 25% of the bacterial strains belong to the family Bacteroides. 如前述請求項中任一項所述之組成物，其中該等細菌菌株中之一或多者屬於擬桿菌屬。The composition according to any one of the preceding claims, wherein one or more of the bacterial strains belong to the genus Bacteroides. 如前述請求項中任一項所述之組成物，其中該組成物不包括屬於擬桿菌目之細菌菌株。The composition according to any one of the preceding claims, wherein the composition does not include a bacterial strain belonging to the order Bacteroides. 如前述請求項中任一項所述之組成物，其中該等細菌菌株中之一或多者為一孢子形成劑。The composition according to any one of the preceding claims, wherein one or more of the bacterial strains are a spore forming agent. 如前述請求項中任一項所述之組成物，其中該等細菌菌株中之一或多者係呈孢子形式。The composition according to any one of the preceding claims, wherein one or more of the bacterial strains are in the form of spores. 如前述請求項中任一項所述之組成物，其中該組成物僅包含絕對厭氧細菌菌株。The composition according to any one of the preceding claims, wherein the composition comprises only an absolutely anaerobic bacterial strain. 如前述請求項中任一項所述之組成物，其中該等細菌菌株中之一或多者不具有一抗生素抗性基因。The composition according to any one of the preceding claims, wherein one or more of the bacterial strains do not have an antibiotic resistance gene. 如前述請求項中任一項所述之組成物，其中該抗生素抗性基因使得該細菌菌株對萬古黴素有抗性。The composition according to any one of the preceding claims, wherein the antibiotic resistance gene renders the bacterial strain resistant to vancomycin. 如前述請求項中任一項所述之組成物，其中該等細菌菌株為人類來源之細菌。The composition according to any one of the preceding claims, wherein the bacterial strains are bacteria of human origin. 如前述請求項中任一項所述之組成物，其中該等細菌菌株係來源於多於一個人類供體。The composition of any preceding claim, wherein the bacterial strains are derived from more than one human donor. 如前述請求項中任一項所述之組成物，其中該組成物誘導CD8+ T細胞之增殖及/或累積。The composition according to any one of the preceding claims, wherein the composition induces proliferation and / or accumulation of CD8 + T cells. 如前述請求項中任一項所述之組成物，其中該組成物為一醫藥組成物。The composition according to any one of the preceding claims, wherein the composition is a pharmaceutical composition. 如前述請求項中任一項所述之醫藥組成物，其中該醫藥組成物包含一醫藥學上可接受的賦形劑。The pharmaceutical composition according to any one of the preceding claims, wherein the pharmaceutical composition comprises a pharmaceutically acceptable excipient. 如前述請求項中任一項所述之醫藥組成物，其中該醫藥組成物係配製用於口服投與。The pharmaceutical composition according to any one of the preceding claims, wherein the pharmaceutical composition is formulated for oral administration. 如前述請求項中任一項所述之醫藥組成物，其中該醫藥組成物係配製用於直腸投與。The pharmaceutical composition according to any one of the preceding claims, wherein the pharmaceutical composition is formulated for rectal administration. 如前述請求項中任一項所述之醫藥組成物，其中該醫藥組成物係配製用於遞送至腸。The pharmaceutical composition according to any one of the preceding claims, wherein the pharmaceutical composition is formulated for delivery to the intestine. 如前述請求項中任一項所述之醫藥組成物，其中該醫藥組成物係配製用於遞送至結腸。The pharmaceutical composition of any one of the preceding claims, wherein the pharmaceutical composition is formulated for delivery to the colon. 如前述請求項中任一項所述之醫藥組成物，其中該等細菌菌株之一或多者係凍乾的。The pharmaceutical composition according to any one of the preceding claims, wherein one or more of the bacterial strains are lyophilized. 如前述請求項中任一項所述之醫藥組成物，其中該醫藥組成物係呈一膠囊形式。The pharmaceutical composition according to any one of the preceding claims, wherein the pharmaceutical composition is in the form of a capsule. 如前述請求項中任一項所述之醫藥組成物，其中該醫藥組成物進一步包含一pH敏感組成物，其包含一或多種腸聚合物。The pharmaceutical composition according to any one of the preceding claims, wherein the pharmaceutical composition further comprises a pH-sensitive composition comprising one or more enteric polymers. 一種包含如前述請求項中任一項所述之組成物及一養分的食物產品。A food product comprising a composition according to any one of the preceding claims and a nutrient. 如前述請求項中任一項所述之組成物，其中該組成物進一步包含一或多種抗癌劑。The composition according to any one of the preceding claims, wherein the composition further comprises one or more anticancer agents. 如前述請求項中任一項所述之組成物，其中該抗癌劑為一化療劑。The composition according to any one of the preceding claims, wherein the anticancer agent is a chemotherapeutic agent. 如前述請求項中任一項所述之組成物，其中該抗癌劑為癌症免疫療法劑。The composition according to any one of the preceding claims, wherein the anticancer agent is a cancer immunotherapy agent. 如前述請求項中任一項所述之組成物，其中該癌症免疫療法劑為一免疫查核點抑制劑。The composition according to any one of the preceding claims, wherein the cancer immunotherapy agent is an immune checkpoint inhibitor. 如前述請求項中任一項所述之組成物，其中該免疫查核點抑制劑為一PD-1抑制劑、PD-L-1抑制劑或CTLA-4抑制劑。The composition according to any one of the preceding claims, wherein the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L-1 inhibitor, or a CTLA-4 inhibitor. 如前述請求項中任一項所述之組成物，其中該免疫查核點抑制劑為一PD-1抑制劑。The composition according to any one of the preceding claims, wherein the immune checkpoint inhibitor is a PD-1 inhibitor. 如前述請求項中任一項所述之組成物，其中該免疫查核點抑制劑為一CTLA-4抑制劑。The composition according to any one of the preceding claims, wherein the immune checkpoint inhibitor is a CTLA-4 inhibitor. 如前述請求項中任一項所述之組成物，其中該組成物進一步包含一或多種細胞介素。The composition of any one of the preceding claims, wherein the composition further comprises one or more cytokines. 如前述請求項中任一項所述之組成物，其中該細胞介素為IL-2、IL-15或IL-21。The composition according to any one of the preceding claims, wherein the interleukin is IL-2, IL-15 or IL-21. 如前述請求項中任一項所述之組成物，其中該組成物進一步包含一或多種共激劑。The composition of any one of the preceding claims, wherein the composition further comprises one or more stimulants. 如前述請求項中任一項所述之組成物，其中該共激劑為一CD-28、OX-40、4-1BB或CD40抗體。The composition according to any one of the preceding claims, wherein the stimulant is a CD-28, OX-40, 4-1BB or CD40 antibody. 如前述請求項中任一項所述之組成物，其中該組成物進一步包含一或多種疫苗。The composition according to any one of the preceding claims, wherein the composition further comprises one or more vaccines. 如前述請求項中任一項所述之組成物，其中該疫苗為一樹狀細胞疫苗。The composition according to any one of the preceding claims, wherein the vaccine is a dendritic cell vaccine. 如前述請求項中任一項所述之組成物，其中該組成物係與授受性細胞轉移療法組合。The composition according to any one of the preceding claims, wherein the composition is combined with an adaptive cell transfer therapy. 如前述請求項中任一項所述之組成物，其中該授受性細胞轉移療法為工程化T細胞受體或嵌合抗原受體之使用。The composition according to any one of the preceding claims, wherein the adaptive cell transfer therapy is the use of an engineered T cell receptor or a chimeric antigen receptor. 一種包含如前述請求項中任一項所述之組成物及一抗原的疫苗。A vaccine comprising a composition according to any one of the preceding claims and an antigen. 如前述請求項中任一項所述之疫苗，其中該抗原為一HIV抗原。The vaccine according to any one of the preceding claims, wherein the antigen is an HIV antigen. 如前述請求項中任一項所述之疫苗，其中該抗原為一肝炎抗原。The vaccine according to any one of the preceding claims, wherein the antigen is a hepatitis antigen. 如前述請求項中任一項所述之組成物，其中該組成物進一步包含一或多種消炎劑。The composition of any one of the preceding claims, wherein the composition further comprises one or more anti-inflammatory agents. 如前述請求項中任一項所述之組成物，其中該消炎劑為一NSAID。The composition according to any one of the preceding claims, wherein the anti-inflammatory agent is an NSAID. 如前述請求項中任一項所述之組成物，其中將該組成物投與至一受試者導致在該受試者之該腸內CD8+ T細胞之增殖及/或累積之誘導。The composition according to any one of the preceding claims, wherein administering the composition to a subject results in induction of proliferation and / or accumulation of CD8 + T cells in the intestine of the subject. 如前述請求項中任一項所述之組成物，其中將該組成物投與至一受試者導致在一受試者之腸內的IFN-γ產生之一增加。The composition of any one of the preceding claims, wherein administering the composition to a subject results in an increase in one of the IFN-γ production in the intestine of a subject. 如前述請求項中任一項所述之組成物，其中將該組成物投與至一受試者導致在該受試者之該腸內該所投與組成物之一或多種細菌菌株之存在。The composition of any one of the preceding claims, wherein administering the composition to a subject results in the presence of one or more bacterial strains of the administered composition in the intestine of the subject . 如前述請求項中任一項所述之組成物，其中該所投與組成物之一或多種細菌菌株先前不存在於該受試者之該腸內。The composition of any one of the preceding claims, wherein one or more bacterial strains of the administered composition have not previously existed in the intestine of the subject. 如前述請求項中任一項所述之組成物，其中將該組成物投與至一受試者導致在該受試者之該腸內該所投與組成物之一或多種細菌菌株之植入。The composition of any one of the preceding claims, wherein administering the composition to a subject results in the planting of one or more bacterial strains of the administered composition in the subject's intestine. Into. 如前述請求項中任一項所述之組成物，其中該所投與組成物之一或多種細菌菌株先前未植入於該受試者之該腸內。The composition of any one of the preceding claims, wherein one or more bacterial strains of the administered composition have not been previously implanted in the intestine of the subject. 如前述請求項中任一項所述之組成物，其中將該組成物投與至一受試者導致在該受試者之該腸內所投與組成物之該等細菌菌株的數量之一增加。The composition of any one of the preceding claims, wherein administering the composition to a subject results in one of the number of bacterial strains of the composition administered in the subject's intestine increase. 如前述請求項中任一項所述之組成物，其中將該組成物投與至一受試者導致植入在該受試者之該腸內的該所投與組成物之該等細菌菌株的該數量之一增加。The composition of any one of the preceding claims, wherein administering the composition to a subject causes the bacterial strains of the administered composition to be implanted in the intestine of the subject One of that number increased. 如前述請求項中任一項所述之組成物，其中將該組成物投與至一受試者導致在該受試者之該腸內該所投與組成物之該等細菌菌株之細菌量之一增加。The composition of any one of the preceding claims, wherein administering the composition to a subject results in a bacterial amount of the bacterial strains of the administered composition in the intestine of the subject One increased. 如前述請求項中任一項所述之組成物，其中將該組成物投與至一受試者導致植入於該受試者之該腸內的該所投與組成物之該等細菌菌株之細菌量之一增加。The composition according to any one of the preceding claims, wherein administering the composition to a subject causes the bacterial strains of the administered composition to be implanted in the intestine of the subject One of the bacteria increased. 一種治療一受試者之一疾病之方法，該方法包含以下步驟：以治療該疾病的一有效量向該受試者投與如前述請求項中任一項所述之組成物。A method of treating a disease in a subject, the method comprising the step of administering to the subject an effective amount of a disease to treat the composition as described in any one of the preceding claims. 如請求項97所述之方法，其中將該組成物投與至該受試者的步驟導致在該受試者之該腸內CD8+ T細胞之增殖及/或累積之誘導。The method according to claim 97, wherein the step of administering the composition to the subject results in induction of proliferation and / or accumulation of CD8 + T cells in the intestine of the subject. 如前述請求項中任一項所述之方法，其中該受試者之該腸內CD8+ T細胞之該增殖及/或累積相較於在該組成物之該投與的步驟之前在該受試者之該腸內CD8+ T細胞之該增殖及/或累積而言增加至少10%、至少20%、至少30%、至少40%、至少50%、至少100%或至少200%。The method of any one of the preceding claims, wherein the subject's intestinal CD8 + T cells proliferate and / or accumulate compared to the subject prior to the step of administering the composition The proliferation and / or accumulation of the intestinal CD8 + T cells is increased by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 100%, or at least 200%. 如前述請求項中任一項所述之方法，其中將該組成物投與至該受試者之步驟導致在相較於在該組成物之該投與的步驟之前該受試者之該腸內的IFN-γ產生時該受試者之該腸內該IFN-γ產生之一增加。The method of any one of the preceding claims, wherein the step of administering the composition to the subject results in the intestine of the subject being compared to the step prior to the step of administering the composition. IFN-γ production within the subject increases one of the IFN-γ production in the intestine of the subject. 如前述請求項中任一項所述之方法，其中將該組成物投與至該受試者之步驟導致在相較於在該組成物之該投與的步驟之前該受試者之該腸內的IFN-γ產生時該受試者之該腸內該IFN-γ產生之一增加，該增加達至少10%、至少20%、至少30%、至少40%、至少50%、至少100%或至少200%。The method of any one of the preceding claims, wherein the step of administering the composition to the subject results in the intestine of the subject being compared to the step prior to the step of administering the composition. IFN-γ production within the subject increases one of the IFN-γ production in the intestine of the subject by an increase of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 100% Or at least 200%. 如前述請求項中任一項所述之方法，其中該受試者患有癌症。The method of any one of the preceding claims, wherein the subject has cancer. 如前述請求項中任一項所述之方法，其中該癌症為惡性腫瘤、神經膠質瘤、間皮瘤、黑素瘤、淋巴瘤、白血病、腺癌、乳癌、卵巢癌、子宮頸癌、神經膠質母細胞瘤、多發性骨髓瘤、前列腺癌、伯基特氏淋巴瘤、頭頸癌、結腸癌、結腸直腸癌、非小細胞肺癌、小細胞肺癌、食管癌、胃癌、胰腺癌、肝膽癌、膽囊癌、小腸癌、直腸癌、腎癌、膀胱癌、前列腺癌、陰莖癌、尿道癌、睾丸癌、陰道癌、子宮癌、甲狀腺癌、副甲狀腺癌、腎上腺癌、胰腺內分泌癌、類癌瘤癌、骨癌、皮膚癌、視網膜母細胞瘤、霍奇金氏淋巴瘤、非霍奇金氏淋巴瘤、卡波西氏肉瘤、多中心Castleman氏病、AIDS相關原發性滲出淋巴瘤、神經外胚層腫瘤或橫紋肌肉瘤。The method according to any one of the preceding claims, wherein the cancer is a malignant tumor, glioma, mesothelioma, melanoma, lymphoma, leukemia, adenocarcinoma, breast cancer, ovarian cancer, cervical cancer, nerve Glioblastoma, multiple myeloma, prostate cancer, Burkitt's lymphoma, head and neck cancer, colon cancer, colorectal cancer, non-small cell lung cancer, small cell lung cancer, esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, Gallbladder cancer, small intestine cancer, rectal cancer, kidney cancer, bladder cancer, prostate cancer, penile cancer, urethral cancer, testicular cancer, vaginal cancer, uterine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, pancreatic endocrine cancer, carcinoid tumor Cancer, bone cancer, skin cancer, retinoblastoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, Kaposi's sarcoma, multicenter Castleman's disease, AIDS-related primary exudative lymphoma, nerve Ectoderm tumor or rhabdomyosarcoma. 如前述請求項中任一項所述之方法，其中該癌症為前列腺癌、膀胱癌、非小細胞肺癌、泌尿上皮細胞惡性腫瘤、黑素瘤或腎細胞惡性腫瘤。The method according to any one of the preceding claims, wherein the cancer is prostate cancer, bladder cancer, non-small cell lung cancer, urinary epithelial cell malignancy, melanoma or renal cell malignancy. 如前述請求項中任一項所述之方法，其中該受試者經歷放射治療。The method of any of the preceding claims, wherein the subject is undergoing radiation therapy. 如前述請求項中任一項所述之方法，其進一步包含以下步驟：投與一或多種抗癌劑。The method of any one of the preceding claims, further comprising the step of administering one or more anticancer agents. 如前述請求項中任一項所述之方法，其中該抗癌劑為一化療劑。The method according to any one of the preceding claims, wherein the anticancer agent is a chemotherapeutic agent. 如前述請求項中任一項所述之方法，其中該抗癌劑為一癌症免疫療法劑。The method according to any one of the preceding claims, wherein the anticancer agent is a cancer immunotherapy agent. 如前述請求項中任一項所述之方法，其中該癌症免疫療法劑為一免疫查核點抑制劑。The method of any one of the preceding claims, wherein the cancer immunotherapy agent is an immune checkpoint inhibitor. 如前述請求項中任一項所述之方法，其中該免疫查核點抑制劑為一PD-1抑制劑、PD-L-1抑制劑或CTLA-4抑制劑。The method according to any one of the preceding claims, wherein the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L-1 inhibitor or a CTLA-4 inhibitor. 如前述請求項中任一項所述之方法，其中該免疫查核點抑制劑為一PD-1抑制劑。The method according to any one of the preceding claims, wherein the immune checkpoint inhibitor is a PD-1 inhibitor. 如前述請求項中任一項所述之方法，其中該免疫查核點抑制劑為一CTLA-4抑制劑。The method according to any one of the preceding claims, wherein the immune checkpoint inhibitor is a CTLA-4 inhibitor. 如前述請求項中任一項所述之方法，其進一步包含以下步驟：投與一或多種細胞介素。The method of any one of the preceding claims, further comprising the step of administering one or more cytokines. 如前述請求項中任一項所述之方法，其中該細胞介素為IL-2、IL-15或IL-21。The method according to any one of the preceding claims, wherein the interleukin is IL-2, IL-15 or IL-21. 如前述請求項中任一項所述之方法，其進一步包含以下步驟：投與一或多種共激劑。The method of any one of the preceding claims, further comprising the step of administering one or more co-stimulants. 如前述請求項中任一項所述之方法，其中該共激劑為一CD-28、OX-40、4-1BB或CD40抗體。The method of any one of the preceding claims, wherein the stimulant is a CD-28, OX-40, 4-1BB or CD40 antibody. 如前述請求項中任一項所述之方法，其進一步包含以下步驟：投與一或多種疫苗。The method of any one of the preceding claims, further comprising the step of administering one or more vaccines. 如前述請求項中任一項所述之方法，其中該疫苗為一樹狀細胞疫苗。The method according to any one of the preceding claims, wherein the vaccine is a dendritic cell vaccine. 如前述請求項中任一項所述之方法，其進一步包含以下步驟：投與授受性細胞轉移療法。The method of any one of the preceding claims, further comprising the step of: administering a recipient cell transfer therapy. 如前述請求項中任一項所述之方法，其中該授受性細胞轉移療法為工程化T細胞受體或嵌合抗原受體之使用。The method of any one of the preceding claims, wherein the adaptive cell transfer therapy is the use of an engineered T cell receptor or a chimeric antigen receptor. 如前述請求項中任一項所述之方法，其中該受試者患有一傳染性疾病。The method of any one of the preceding claims, wherein the subject has an infectious disease. 如前述請求項中任一項所述之方法，其中該傳染性疾病為一細菌感染、一病毒感染、一寄生蟲感染或一真菌感染。The method according to any one of the preceding claims, wherein the infectious disease is a bacterial infection, a viral infection, a parasitic infection, or a fungal infection. 如前述請求項中任一項所述之方法，其中該傳染性疾病為一病毒感染。The method according to any one of the preceding claims, wherein the infectious disease is a viral infection. 如前述請求項中任一項所述之方法，其中該病毒感染為HIV。The method of any one of the preceding claims, wherein the virus is infected with HIV. 如前述請求項中任一項所述之方法，其中該受試者患有一自體免疫疾病或一過敏性疾病。The method of any one of the preceding claims, wherein the subject has an autoimmune disease or an allergic disease. 如前述請求項中任一項所述之方法，其中該組成物進一步包含一或多種消炎劑。The method of any one of the preceding claims, wherein the composition further comprises one or more anti-inflammatory agents. 如前述請求項中任一項所述之方法，其中該消炎劑為一NSAID。The method according to any one of the preceding claims, wherein the anti-inflammatory agent is an NSAID. 如前述請求項中任一項所述之方法，其中該組成物係以多於一種劑量投與。The method of any of the preceding claims, wherein the composition is administered in more than one dose. 一種方法，該方法包含以下步驟 判定如前述請求項中任一項所述之組成物之一或多種細菌物種是否存在於一受試者之腸內， 其中若存在小於100%、小於90%、小於80%、小於70%、小於60%、小於50%、小於40%、小於30%、小於20%、小於10%之該等細菌物種，或不存在該等細菌物種，則將該組成物投與至該受試者。A method comprising the steps of determining whether one or more bacterial species of the composition according to any one of the preceding claims is present in the intestine of a subject, wherein if present is less than 100%, less than 90%, Less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10% of these bacterial species, or the absence of such bacterial species, the composition Administration to the subject. 一種用於執行如請求項129所述之伴隨式診斷方法的套組，其包含判定如前述請求項中任一項所述之組成物之一或多種細菌物種是否存在於一受試者之腸內。A kit for performing the companion diagnostic method according to claim 129, comprising determining whether one or more bacterial species of the composition according to any one of the preceding claims is present in the intestine of a subject Inside. 如請求項130所述之方法，其中癌症治療為癌症免疫療法治療。The method of claim 130, wherein the cancer treatment is a cancer immunotherapy treatment. 如前述請求項中任一項所述之方法，其中該受試者經歷或將經歷癌症治療。The method of any one of the preceding claims, wherein the subject undergoes or will undergo cancer treatment. 一種用於判定是否預期一受試者對癌症治療積極反應的方法，該方法包含以下步驟 判定如前述請求項中任一項所述之組成物之一或多種細菌物種是否存在於一受試者之腸內，其中若存在小於100%、小於90%、小於80%、小於70%、小於60%、小於50%、小於40%、小於30%、小於20%、小於10%之該等細菌物種，或不存在該等細菌物種，則不預期該受試者對癌症治療積極反應。A method for determining whether a subject is expected to respond positively to cancer treatment, the method comprising the steps of determining whether one or more bacterial species of the composition according to any one of the preceding claims are present in a subject In the intestine, if there is less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10% Species, or the absence of such bacterial species, the subject is not expected to respond positively to cancer treatment. 一種用於降低一受試者的一病毒感染之風險的方法，該方法包含以下步驟 判定如前述請求項中任一項所述之組成物之一或多種細菌物種是否存在於一受試者之腸內，其中若存在小於100%、小於90%、小於80%、小於70%、小於60%、小於50%、小於40%、小於30%、小於20%、小於10%之該等細菌物種，或不存在該等細菌物種，則將該組成物投與至受試者，進而降低該受試者的一病毒感染之該風險。A method for reducing the risk of a viral infection in a subject, the method comprising the steps of determining whether one or more bacterial species of the composition according to any one of the preceding claims is present in a subject In the intestine, if there are less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10% , Or the absence of such bacterial species, the composition is administered to the subject, thereby reducing the risk of a viral infection in the subject. 如前述請求項中任一項所述之方法，其中判定該等細菌物種中之一或多者之該存在的步驟係藉由將該受試者之糞便物測序來進行。The method of any one of the preceding claims, wherein the step of determining the presence of one or more of the bacterial species is performed by sequencing the subject's fecal matter. 如前述請求項中任一項所述之方法，其中判定該等細菌物種中之一或多者之該存在的步驟係藉由將該受試者之糞便物之該等16S rDNA序列測序來進行。The method of any one of the preceding claims, wherein the step of determining the presence of one or more of the bacterial species is performed by sequencing the 16S rDNA sequences of the subject's fecal matter . 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含一或多種細菌菌株，該等細菌菌株包含與以下NCBI登錄號之序列具有至少95%同源性之16S rDNA序列：LN998073、KR822463、CP011531、NR_112945、NZ-ACWW00000000、AB331897、AB261128、NZ-CAEG00000000、AB470343、AB595134、HE974920、NR_112933、AB490801、NZ-ACWB00000000、AY608696、CR626927、AB247141、NR_112935、AB249652、NR_113076或AF139525。A composition comprising a purified bacterial mixture comprising one or more bacterial strains comprising a 16S rDNA sequence having at least 95% homology with the sequence of the following NCBI accession number: LN998073, KR822463, CP011531 , NR_112945, NZ-ACWW00000000, AB331897, AB261128, NZ-CAEG00000000, AB470343, AB595134, HE974920, NR_112933, AB490801, NZ-ACWB00000000, AY608696, CR626927, AB247141, NR_112935, AB249652, NR_113076 or AF139525. 如請求項137所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。The composition of claim 137, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains. 如請求項137或請求項138所述之組成物，其中該一或多個細菌菌株包含與該等登錄號之該等序列具有至少96%、至少97%、至少98%或至少99%同源性之16S rDNA序列。The composition of claim 137 or claim 138, wherein the one or more bacterial strains contain at least 96%, at least 97%, at least 98%, or at least 99% homology to the sequences of the accession numbers 16S rDNA sequence. 一種誘導或活化產生CD8+ IFNγ之T細胞的組成物，該組成物包含 i 自人類糞便收集的擁有對安比西林之抗性的一或多種純化細菌菌株；或ii (i)之一培養上清液。A composition for inducing or activating CD8 + IFNγ-producing T cells, the composition comprising: i. One or more purified bacterial strains having resistance to ampicillin collected from human feces; or ii (i) a culture supernatant . 如請求項140所述之組成物，其中該組成物包含一純化細菌混合物，該純化細菌混合物包含(a)屬於選自由以下各項組成之群的一物種之一或多種細菌菌株： 糞考拉桿菌；LN998073，潰瘍梭桿菌；KR822463，多利擬桿菌；CP011531，單形擬桿菌；NR_112945，罕見小球菌屬4_3_54A2FAA；NZ-ACWW00000000，Paraprevotella xylaniphila；AB331897，約氏副擬桿菌；AB261128，別樣桿菌屬JC136；NZ-CAEG00000000，戈登副擬桿菌；AB470343，黏真桿菌；AB595134，狄氏副擬桿菌；HE974920，解纖維素擬桿菌；NR_112933，克拉氏擬桿菌；AB490801，厭氧棒狀菌屬3_2_56FAA；NZ-ACWB00000000，塞爾氏擬桿菌；AY608696，脆弱擬桿菌；CR626927，單形擬桿菌；AB247141，埃氏擬桿菌；NR_112935，梭菌屬TM-40；AB249652，古氏副擬桿菌；NR_113076，及擬桿菌屬AR29；AF139525；或(b)一或多種細菌菌株，該等細菌菌株包含與選自由以下各項組成之群的一物種之一16S rRNA序列具有至少97%同源性之一16S rRNA序列：糞考拉桿菌；LN998073，潰瘍梭桿菌；KR822463，多利擬桿菌；CP011531，單形擬桿菌；NR_112945，罕見小球菌屬4_3_54A2FAA；NZ-ACWW00000000， Paraprevotella xylaniphila；AB331897， 約氏副擬桿菌；AB261128，別樣桿菌屬JC136；NZ-CAEG00000000，戈登副擬桿菌；AB470343，黏真桿菌；AB595134，狄氏副擬桿菌；HE974920，解纖維素擬桿菌；NR_112933，克拉氏擬桿菌；AB490801，厭氧棒狀菌屬3_2_56FAA；NZ-ACWB00000000，塞爾氏擬桿菌；AY608696，脆弱擬桿菌；CR626927，單形擬桿菌；AB247141，埃氏擬桿菌；NR_112935，梭菌屬TM-40；AB249652，古氏副擬桿菌；NR_113076，及擬桿菌屬AR29；AF139525。The composition of claim 140, wherein the composition comprises a purified bacterial mixture comprising (a) one or more bacterial strains belonging to a species selected from the group consisting of: fecal koalas Bacillus; LN998073, Clostridium ulcerans; KR822463, Bacteroides dorisi; CP011531, Bacteroides spp .; NR_112945, Rare micrococcus 4_3_54A2FAA; NZ-ACWW00000000, Paraprevotella xylaniphila; AB331897, Parabacillus yojei; AB261128, Allobacterium JC136; NZ-CAEG00000000, Pseudomonas gordonii; AB470343, Pseudomonas myxobacteria; AB595134, Pseudomonas diescherii; HE974920, Bacteroides cellulolyticus; NR_112933, Pseudomonas cladii; AB490801, Corynebacterium anaerobic 3_2_56FAA ; NZ-ACWB00000000, Bacteroides seri; AY608696, Bacteroides fragile; CR626927, Bacteroides morphogenes; AB247141, Bacteroides escherichia; NR_112935, Clostridium TM-40; AB249652, B. archaea; NR_113076, And Bacteroides AR29; AF139525; or (b) one or more bacterial strains comprising and selected from the group consisting of One of the species' 16S rRNA sequence has at least 97% homology. One of the 16S rRNA sequences: Koala faecalis; LN998073, Clostridium ulcerans; KR822463, Bacteroides dorsii; CP011531, Bacteroides monomorphum; NR_112945, Rare micrococcus 4_3_54A2FAA ; NZ-ACWW00000000, Paraprevotella xylaniphila; AB331897, Bacteroides yojei; AB261128, Pseudomonas genus JC136; NZ-CAEG00000000, Pseudomonas gordonii; AB470343, Myxobacteria; AB595134, Pseudomonas dickii; HE974920, Cellulolytic Bacterium; NR_112933, Bacteroides clarkii; AB490801, Anaerobic corynebacterium 3_2_56FAA; NZ-ACWB00000000, Bacteroides selenoides; AY608696, Bacteroides fragile; CR626927, Bacteroides monomorph; AB247141, Escherichia Bacteroides; NR_112935, Clostridium TM-40; AB249652, B. archaea; NR_113076, and Bacteroides AR29; AF139525. 如請求項140所述之組成物，其中該組成物包含一純化細菌混合物，該純化細菌混合物包含(a)屬於選自由以下各項組成之群的一物種之一或多種細菌菌株： 糞考拉桿菌；LN998073 潰瘍梭桿菌；KR822463，多利擬桿菌；CP011531，單形擬桿菌；NR_112945，罕見小球菌屬4_3_54A2FAA；NZ-ACWW00000000，Paraprevotella xylaniphila；AB331897，約氏副擬桿菌；AB261128，別樣桿菌屬JC136；NZ-CAEG00000000，戈登副擬桿菌；AB470343，黏真桿菌；AB595134，及狄氏副擬桿菌；HE974920；或(b)一或多種細菌菌株，該等細菌菌株包含與屬於由以下各項組成之群的一物種之一16S rRNA序列具有至少97%同源性之一16S rRNA序列：糞考拉桿菌；LN998073 潰瘍梭桿菌；KR822463，多利擬桿菌；CP011531，單形擬桿菌；NR_112945，罕見小球菌屬4_3_54A2FAA；NZ-ACWW00000000，Paraprevotella xylaniphila；AB331897，約氏副擬桿菌；AB261128，別樣桿菌屬JC136；NZ-CAEG00000000，戈登副擬桿菌；AB470343，黏真桿菌；AB595134，及狄氏副擬桿菌；HE974920。The composition of claim 140, wherein the composition comprises a purified bacterial mixture comprising (a) one or more bacterial strains belonging to a species selected from the group consisting of: fecal koalas Bacillus; LN998073 Clostridium ulcerans; KR822463, Bacteroides dorisi; CP011531, Bacteroides spp .; NR_112945, Rare micrococcus 4_3_54A2FAA; NZ-ACWW00000000, Paraprevotella xylaniphila; AB331897, Parabacter yojei; AB261128, Albicans NZ-CAEG00000000, B. gordonii; AB470343, Bacteroides mucus; AB595134, and B. dickii; HE974920; or (b) one or more bacterial strains, which include and belong to the following: One 16S rRNA sequence of one species in the group has at least 97% homology. One of the 16S rRNA sequences: Koala faecalis; LN998073 Clostridium ulcerans; KR822463, Bacteroides doris; CP011531, Bacteroides monomorphum; NR_112945, rare small 4_3_54A2FAA; NZ-ACWW00000000, Paraprevotella xylaniphila; AB331897, Pseudomonas yojei; AB261128, Isobacterium JC1 36; NZ-CAEG00000000, B. gordonii; AB470343, Bacteroides mucus; AB595134, and B. dickii; HE974920. 如請求項140-142中任一項所述之組成物，其中該產生CD8+ IFNγ之T細胞表現CD103或顆粒酶B。The composition according to any one of claims 140 to 142, wherein the CD8 + IFNγ producing T cell expresses CD103 or granzyme B. 如請求項140-143中任一項所述之組成物，其中該組成物活化免疫系統。The composition of any one of claims 140-143, wherein the composition activates the immune system. 一種用於活化免疫系統之方法，該方法包含以下步驟：向一受試者投與如請求項140-144中任一項所述之組成物。A method for activating the immune system, the method comprising the step of administering to a subject a composition as described in any one of claims 140-144. 一種用於活化產生CD8+ IFN-γ之T細胞的方法，該方法包含以下步驟向一受試者投與如請求項140-144中任一項所述之組成物。A method for activating CD8 + IFN-γ-producing T cells, the method comprising the steps of administering to a subject a composition as described in any one of claims 140-144. 一種用於在腸內誘導CD8+ T細胞之增殖及/或累積的方法，該方法包含以下步驟：向一受試者投與如請求項140-144中任一項所述之組成物，其中該投與的步驟導致在該受試者之該腸內CD8+ T細胞之增殖及/或累積之該誘導。A method for inducing the proliferation and / or accumulation of CD8 + T cells in the intestine, the method comprising the steps of administering to a subject a composition according to any one of claims 140-144, wherein the The step of administering results in the induction of proliferation and / or accumulation of CD8 + T cells in the intestine of the subject. 一種用於治療、輔助治療及/或預防癌症或病毒感染的方法，該方法包含以下步驟：向一受試者投與如請求項140-143中任一項所述之組成物，其中該投與的步驟導致癌症或病毒感染之該治療、輔助治療及/或預防。A method for the treatment, adjuvant treatment and / or prevention of a cancer or viral infection, the method comprising the steps of administering to a subject a composition according to any one of claims 140-143, wherein the administering And the steps lead to such treatment, adjuvant treatment and / or prevention of cancer or viral infection. 一種疫苗組成物，其含有來源於如請求項140-144中之任一項所述之組成物的該等細菌物種之成分及/或代謝物的一抗原。A vaccine composition comprising an antigen derived from components and / or metabolites of the bacterial species derived from the composition according to any one of claims 140-144. 一種用於誘導一受試者之一免疫反應的方法，該方法包含以下步驟：向該受試者投與如請求項149所述之疫苗組成物，其中該投與的步驟導致該受試者之一免疫反應之該誘導。A method for inducing an immune response in a subject, the method comprising the steps of administering to the subject a vaccine composition as described in claim 149, wherein the step of administering results in the subject The induction of an immune response. 一種組成物，其包含擁有針對如請求項140-144中任一項所述之組成物之任何該等細菌物種的一抗菌活性的一化學物質，或結合自如請求項140-144中任一項所述之組成物之任何該等細菌物種分泌的一生理學活性物質之一化學物質。A composition comprising a chemical substance having an antibacterial activity against any of these bacterial species of the composition according to any one of claims 140-144, or a combination of any one of claims 140-144 A chemical substance that is a physiologically active substance secreted by any of these bacterial species of the composition described. 一種用於抑制一受試者體內的產生CD8+及IFNγ之T細胞的方法，該方法包含以下步驟：向該受試者投與如請求項151所述之組成物。A method for inhibiting CD8 + and IFNγ-producing T cells in a subject, the method comprising the step of administering to the subject a composition as described in claim 151. 一種用於預防、治療或改良因一受試者之產生CD8+及IFNγ之T細胞的過活化而引起的一疾病之方法，該方法包含以下步驟：向該受試者投與投與如請求項151所述之組成物。A method for preventing, treating or ameliorating a disease caused by the over-activation of CD8 + and IFNγ-producing T cells in a subject, the method comprising the steps of administering to the subject administration The composition of 151. 一種來源於如請求項140-144中任一項所述之一細菌物種的生理學活性物質。A physiologically active substance derived from a bacterial species according to any one of claims 140-144. 一種如請求項140-144中任一項所述之細菌物種之任一者之細菌特異性抗原。A bacterial-specific antigen of any of the bacterial species as described in any one of claims 140-144. 一種抗體，其特異地結合如請求項140-144中任一項所述之細菌物種之任一者。An antibody that specifically binds to any one of the bacterial species as described in any one of claims 140-144. 一種用於偵測如請求項140-144中任一項所述之細菌物種之任一者的一細菌特異性核苷酸序列的多核苷酸。A polynucleotide for detecting a bacterial-specific nucleotide sequence of any of the bacterial species according to any one of claims 140-144. 一種包含一非人類哺乳動物之動物模型，其中該非人類哺乳動物之腸道已利用如請求項140-144中任一項所述之細菌物種接種。An animal model comprising a non-human mammal, wherein the intestinal tract of the non-human mammal has been inoculated with a bacterial species as described in any one of claims 140-144. 如請求項158所述之動物模型，其中該非人類哺乳動物患有由產生CD8+ IFNγ之T細胞之不規則性引起的一疾病。The animal model of claim 158, wherein the non-human mammal has a disease caused by irregularities in CD8 + IFNγ producing T cells. 一種用於評估產生T細胞之CD8+ IFNγ之活化的套組，該套組包含：腸上皮細胞、末梢血液單核細胞及如請求項140-144中任一項所述之細菌物種。A kit for evaluating the activation of CD8 + IFNγ producing T cells, the kit comprising: intestinal epithelial cells, peripheral blood mononuclear cells, and a bacterial species according to any one of claims 140-144. 一種用於篩選來源於人類腸細菌之一生理學活性物質或細菌的方法，其中該物質誘導該腸道內產生CD8+ IFNγ之T細胞之活化，該方法包含以下步驟 i. 使一非人類無菌動物攝取來源於人類腸細菌之一生理學活性物質或細菌，ii. 偵測該非人類無菌動物之該腸道內產生CD8+IFNγ之T細胞之數量或活性，其中若偵測到產生CD8+ IFNγ之T細胞之活化，則該生理學活性物質係識別為可活化產生CD8+ IFNγ之T細胞之一物質。A method for screening a physiologically active substance or bacterium derived from a human intestinal bacterium, wherein the substance induces the activation of CD8 + IFNγ-producing T cells in the intestine, the method comprising the following steps i. Ingestion of a non-human sterile animal Derived from a physiologically active substance or bacteria of human intestinal bacteria, ii. Detecting the number or activity of CD8 + IFNγ producing T cells in the intestine of the non-human sterile animal, wherein if CD8 + IFNγ producing T cells are detected When activated, the physiologically active substance is recognized as one of the T cells that can activate CD8 + IFNγ production. 一種用於篩選來源於人類腸細菌之一生理學活性物質或細菌的方法，其中該物質誘導該腸道內產生CD8+ IFNγ之T細胞之增殖或活化，該方法包含以下步驟 i. 將來源於人類腸細菌之一生理學活性物質或細菌添加至包含腸上皮細胞及末梢血液單核細胞之一系統中之該等腸上皮細胞，ii. 偵測該系統中產生CD8+ IFNγ之T細胞之數量或活性，其中若偵測到產生CD8+ IFNγ之T細胞之該活化，則該生理學活性物質係識別為可活化產生CD8+ IFNγ之T細胞之一物質。A method for screening a physiologically active substance or bacteria derived from a human intestinal bacterium, wherein the substance induces the proliferation or activation of CD8 + IFNγ-producing T cells in the intestine, the method comprising the following steps i. A physiologically active substance of bacteria or bacteria is added to the intestinal epithelial cells in a system including intestinal epithelial cells and peripheral blood mononuclear cells, ii. Detecting the number or activity of T cells that produce CD8 + IFNγ in the system, wherein If the activation of CD8 + IFNγ-producing T cells is detected, the physiologically active substance is identified as a substance that can activate CD8 + IFNγ-producing T cells. 一種用於篩選在腸道內誘導產生CD8+ IFNγ之T細胞之活化的一物質的方法，該方法包含以下步驟： i. 將來源於細菌或如請求項140-144中任一項所述之組成物中含有的細菌之一生理學活性物質添加至含有腸上皮細胞及末梢血液單核細胞之一系統，ii. 添加一測試物質，iii. 偵測該系統中產生CD8+ IFNγ之T細胞之數量或活性，其中若偵測到的產生CD8+ IFNγ之T細胞之該數量或活性增加，則測試物質係識別為誘導產生CD8+IFNγ之T細胞之活化的一物質。A method for screening a substance that induces the activation of CD8 + IFNγ-producing T cells in the intestine, the method comprising the steps of: i. Deriving from a bacterium or a composition as described in any one of claims 140-144 A physiologically active substance of bacteria contained in the system is added to a system containing intestinal epithelial cells and peripheral blood mononuclear cells, ii. Adding a test substance, iii. Detecting the number or activity of T cells that produce CD8 + IFNγ in the system If the number or activity of CD8 + IFNγ-producing T cells is detected to increase, the test substance is identified as a substance that induces the activation of CD8 + IFNγ-producing T cells. 一種用於篩選在腸道內誘導產生CD8+ IFNγ之T細胞之活化的一物質的方法，該方法包含以下步驟： i. 將一測試物質添加至如請求項159所述之非人類動物，ii. 偵測該非人類動物之該腸道內產生CD8+ IFNγ之T細胞之數量或活性，其中若在該上文步驟中偵測到的產生CD8+ IFNγ之T細胞之該數量或活性增加，則測試物質係識別為誘導產生CD8+IFNγ之T細胞之活化的一物質。A method for screening a substance that induces the activation of CD8 + IFNγ-producing T cells in the intestine, the method comprising the steps of: i. Adding a test substance to a non-human animal as described in claim 159, ii. Detecting the number or activity of CD8 + IFNγ-producing T cells in the intestine of the non-human animal, wherein if the number or activity of CD8 + IFNγ-producing T cells detected in the above step is increased, the test substance is Recognized as a substance that induces the activation of CD8 + IFNγ producing T cells. 一種用於刺激免疫性之組成物，該組成物包含作為一活性成分之一人類腸細菌或來源於藉由如請求項161-164中任一項所述之篩選方法獲得的一細菌之一生理學活性物質。A composition for stimulating immunity, the composition comprising a human intestinal bacterium as an active ingredient or a physiology derived from a bacterium obtained by the screening method according to any one of claims 161-164 Active substance. 如請求項165所述之組成物，其中該組成物誘導產生CD8+ IFNγ之T細胞之該活化。The composition of claim 165, wherein the composition induces the activation of CD8 + IFNγ-producing T cells. 一種疫苗組成物，其包含作為一活性成分的藉由如請求項161-164中任一項所述之篩選方法獲得的一或多種人類腸細菌，或對該一或多種人類腸細菌特異的一或多種抗原。A vaccine composition comprising, as an active ingredient, one or more human intestinal bacteria obtained by the screening method according to any one of claims 161-164, or one specific to the one or more human intestinal bacteria. Or multiple antigens. 一種用於篩選一物質之方法，該物質具有誘導或惡化由產生CD8+ IFNγ之T細胞所引起的一疾病之一活性，該方法包含以下步驟 i. 允許一測試物質藉由如請求項158所述之非人類動物攝取，ii. 偵測在該非人類動物體內由產生CD8+ IFNγ之T細胞所引起的一疾病相關破壞之程度，其中在該上文步驟中偵測到的損害程度相較於不添加化合物或安慰劑時增加時，該測試物質係識別為誘導由產生CD8+ IFNγ之T細胞所引起的一疾病之一物質。A method for screening a substance having the activity of inducing or aggravating a disease caused by CD8 + IFNγ producing T cells, the method comprising the following steps i. Allowing a test substance to be used as described in claim 158 Uptake of non-human animals, ii. Detecting the extent of a disease-related damage caused by CD8 + IFNγ-producing T cells in the non-human animal, wherein the degree of damage detected in the above step is greater than that without addition When the compound or placebo is increased, the test substance is recognized as one of substances that induces a disease caused by CD8 + IFNγ producing T cells. 一種用於誘導或惡化由產生CD8+ IFNγ之T細胞所引起的一疾病之組成物，其中該組成物包含作為一活性成分之藉由如請求項168所述之篩選方法獲得的物質。A composition for inducing or exacerbating a disease caused by CD8 + IFNγ producing T cells, wherein the composition comprises, as an active ingredient, a substance obtained by the screening method according to claim 168. 一種包含一經處理人類糞便樣本之組成物，其中該經處理人類糞便樣本係藉由使一人類糞便樣本與一有效量之安比西林接觸來獲得，且其中該經處理人類糞便樣本誘導CD8+ T細胞之增殖及/或累積。A composition comprising a processed human stool sample, wherein the processed human stool sample is obtained by contacting a human stool sample with an effective amount of ampicillin, and wherein the processed human stool sample induces CD8 + T cells. Proliferation and / or accumulation. 一種治療一受試者之一疾病之方法，該方法包含以下步驟：以治療該受試者之該疾病的一有效量向該受試者投與如請求項170所述之組成物。A method of treating a disease in a subject, the method comprising the step of administering to the subject a composition as described in claim 170 in an effective amount to treat the disease in the subject. 如請求項171所述之方法，其中該疾病為一癌症或一感染。The method of claim 171, wherein the disease is a cancer or an infection. 一種用於判定一人類糞便樣本是否誘導CD8+ T細胞之增殖及/或累積的方法，該方法包含以下步驟： 利用一人類糞便樣本接種無菌小鼠，及判定該人類糞便樣本是否在該無菌小鼠體內誘導CD8+ T細胞之該增殖及/或累積。A method for determining whether a human stool sample induces the proliferation and / or accumulation of CD8 + T cells, the method comprises the following steps: inoculating a sterile mouse with a human stool sample, and determining whether the human stool sample is in the sterile mouse This proliferation and / or accumulation of CD8 + T cells is induced in vivo. 一種用於識別一人類糞便供體之方法，該方法包含以下步驟： 利用一人類受試者之一糞便樣本接種無菌小鼠，及判定該糞便樣本是否誘導CD8+ T細胞之該增殖及/或累積，其中若該糞便樣本誘導CD8+ T細胞之該增殖及/或累積，則該人類受試者係識別為一人類糞便供體。A method for identifying a human stool donor, the method comprising the steps of: inoculating a sterile mouse with a stool sample of a human subject, and determining whether the stool sample induces the proliferation and / or accumulation of CD8 + T cells If the fecal sample induces the proliferation and / or accumulation of CD8 + T cells, the human subject is identified as a human fecal donor. 一種用於分析一受試者之淋巴細胞中一標誌物之表現位準的方法，該方法包含以下步驟 分析該標誌物之該表現位準，其中該標誌物係藉由向該受試者投與如請求項140-144中任一項所述之組成物來誘導，其中該標誌物為CD44、gp70 MC38肽(KSPWFTTL；(SEQ ID NO:53))特異性TCR、腫瘤抗原源配位體特異性TCR、CD8、IFNγ及/或GzmB。A method for analyzing the performance level of a marker in a subject's lymphocytes, the method comprising the steps of analyzing the performance level of the marker, wherein the marker is administered to the subject by Induced with the composition according to any one of claims 140-144, wherein the marker is a CD44, gp70 MC38 peptide (KSPWFTTL; (SEQ ID NO: 53)) specific TCR, a tumor antigen-derived ligand Specific TCR, CD8, IFNγ and / or GzmB. 一種用於分析在誘導之後一受試者之淋巴細胞中之一標誌物的表現位準的套組，其中該標誌物係藉由向該受試者投與如請求項140-144中任一項所述之組成物來誘導，其中該標誌物為CD44、gp70 MC38肽(KSPWFTTL；(SEQ ID NO ：53))特異性TCR、腫瘤抗原源配位體特異性TCR、CD8、IFNγ及/或GzmB。A set for analyzing the performance level of a marker in a subject's lymphocytes after induction, wherein the marker is administered to the subject by any of claims 140-144 Induced by the composition described in the above item, wherein the marker is CD44, gp70 MC38 peptide (KSPWFTTL; (SEQ ID NO: 53)) specific TCR, tumor antigen source ligand specific TCR, CD8, IFNγ and / or GzmB. 一種篩選用於來源於人類腸細菌之一生理學活性物質或細菌的方法，該方法包含以下步驟： 使一帶腫瘤非人類動物攝取來源於人類腸細菌之一生理學活性物質或細菌，偵測自該帶腫瘤非人類動物分離的淋巴細胞中之一標誌物之表現，其中若偵測到該標誌物之表現位準的一增加，則該生理學活性物質係識別為用於該腫瘤之一免疫刺激劑；及其中該標誌物為CD44、gp70 MC38肽(KSPWFTTL；(SEQ ID NO:53))特異性TCR、腫瘤抗原源配位體特異性TCR、CD8、IFNγ及/或GzmB。A method for screening a physiologically active substance or bacteria derived from a human intestinal bacterium, the method comprising the following steps: a region of a tumor non-human animal ingests a physiologically active substance or bacteria derived from a human intestinal bacterium, and detects from the region The expression of a marker in a lymphocyte isolated from a non-human animal of a tumor, wherein if an increase in the expression level of the marker is detected, the physiologically active substance is identified as an immunostimulant for the tumor And the marker is CD44, gp70 MC38 peptide (KSPWFTTL; (SEQ ID NO: 53))-specific TCR, tumor antigen-derived ligand-specific TCR, CD8, IFNγ, and / or GzmB. 一種用於利用一免疫查核點抑制劑之腫瘤療法的伴隨式診斷方法，該方法包含以下步驟 分析在藉由具有或不具有該免疫查核點抑制劑之共同投與的情況下向該受試者投與如請求項140-144中任一項所述之組成物進行誘導之前及之後淋巴細胞中之一標誌物之表現位準，其中若該受試者之該等淋巴細胞中之該標誌物的該等表現位準相較於在向該受試者投與該組成物，共同投與該抑制劑及如請求項140-144中任一項所述之組成物之前該受試者之該等淋巴細胞中之該等表現位準增加達至少10%、至少20%、至少30%至少40%、至少50%、至少100%或至少200%，則該療法繼續，其中若該受試者之該等淋巴細胞中之該等表現位準相較於該受試者之該等淋巴細胞中之該等表現位準不增加，則中斷該抑制劑及如請求項140-144中任一項所述之組成物之共同投與，或在重複將如請求項140-144中任一項所述之組成物投與至該受試者之後重新分析。A companion diagnostic method for tumor therapy using an immune checkpoint inhibitor, the method comprising the steps of analyzing the subject with or without co-administration of the immune checkpoint inhibitor to the subject The level of performance of one of the markers in lymphocytes before and after administration of a composition as described in any one of claims 140-144, wherein if the marker is in the lymphocytes of the subject The levels of performance of this subject are compared to those of the subject prior to administration of the composition to the subject, co-administration of the inhibitor and composition as described in any one of claims 140-144 If the performance levels in lymphocytes increase by at least 10%, at least 20%, at least 30% at least 40%, at least 50%, at least 100%, or at least 200%, the therapy continues, and if the subject The performance levels in the lymphocytes are not increased compared to the performance levels in the lymphocytes of the subject, the inhibitor is discontinued and if any of the claims 140-144 Co-administration of the stated composition, or in a repetition of The composition according to any one is administered to the subject and reanalyzed. 如請求項175、177或178中任一項所述之方法，其進一步包含以下步驟：利用結合至腫瘤抗原源配位體特異性TCR之特異性抗體或結合至腫瘤抗原源配位體特異性TCR之MHC單體集合體分析淋巴細胞中之該腫瘤抗原源配位體特異性TCR之表現位準。The method of any one of claims 175, 177, or 178, further comprising the step of using a specific antibody bound to a tumor antigen-derived ligand-specific TCR or a tumor antigen-derived ligand-specific The MHC monomer assembly of TCR was used to analyze the expression level of the tumor antigen-derived ligand-specific TCR in lymphocytes. 如請求項179所述之方法，其適用於利用一免疫查核點抑制劑之一腫瘤療法，其中該免疫查核點抑制劑為一PD-1抑制劑、PD-L1抑制劑或CTLA-4抑制劑。The method according to claim 179, which is applicable to tumor therapy using an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor . 如請求項179所述之方法，其進一步包含以下步驟評定該受試者之T細胞中的PD-1表現。The method of claim 179, further comprising the step of assessing PD-1 expression in T cells of the subject. 如請求項179所述之方法，其進一步包含以下步驟評定該受試者之癌細胞中的PD-L1表現。The method of claim 179, further comprising the step of assessing PD-L1 expression in the cancer cells of the subject. 如請求項179所述之方法，其進一步包含以下步驟評定該受試者之T細胞中的CTLA-4表現。The method of claim 179, further comprising the step of assessing CTLA-4 performance in the T cells of the subject. 一種包含如請求項177-183中任一項所述之伴隨式診斷的套組，其中該套組包含用於監視淋巴細胞中之一標誌物之表現位準的一或多種分子，其中該標誌物為CD44、gp70 MC38肽(KSPWFTTL；(SEQ ID NO:53))特異性TCR、腫瘤抗原源配位體特異性TCR、CD8、IFNγ及/或GzmB。A kit comprising an adjoint diagnosis according to any one of claims 177-183, wherein the kit comprises one or more molecules for monitoring the performance level of a marker in a lymphocyte, wherein the marker The compounds are CD44, gp70 MC38 peptide (KSPWFTTL; (SEQ ID NO: 53))-specific TCR, tumor antigen-derived ligand-specific TCR, CD8, IFNγ, and / or GzmB. 一種用於利用脾細胞中之IFNγ產生程度來評估免疫活化之方法，該方法包含以下步驟：向一受試者投與如請求項140-144中任一項所述之組成物。A method for assessing immune activation by utilizing the degree of IFNγ production in spleen cells, the method comprising the steps of administering to a subject a composition as described in any one of claims 140-144. 一種用於利用脾細胞中IFNγ產生程度來評估免疫活化之套組， 該套組包含：一或多種IFNγ標誌物分子及如請求項140-144中任一項所述之一或多種細菌物種。A kit for assessing immune activation by utilizing the degree of IFNγ production in spleen cells, the kit comprising: one or more IFNγ marker molecules and one or more bacterial species according to any one of claims 140-144. 一種用於識別用於一腫瘤之一免疫刺激劑的方法，該方法係藉由篩選一人類腸細菌或來源於人類腸細菌之一生理學活性物質來達成，該方法包含以下步驟 (i) 使一帶腫瘤非人類動物攝取該人類腸細菌或來源於該人類腸細菌之該生理學活性物質，及(ii) 偵測自該帶腫瘤非人類動物分離的脾細胞中之IFNγ，其中若偵測到IFNγ之誘導，則該人類腸細菌或生理學活性物質係識別為用於該腫瘤之一免疫刺激劑。A method for identifying an immunostimulant for a tumor. The method is achieved by screening a human intestinal bacterium or a physiologically active substance derived from a human intestinal bacterium. The method includes the following steps (i): The tumor non-human animal ingests the human intestinal bacteria or the physiologically active substance derived from the human intestinal bacteria, and (ii) detects IFNγ in spleen cells isolated from the tumor-free non-human animal, where IFNγ is detected Induction, the human intestinal bacteria or physiologically active substance is recognized as an immunostimulant for the tumor. 一種用於利用一免疫查核點抑制劑之腫瘤療法的伴隨式診斷方法，該方法包含以下步驟 在藉由具有或不具有該抑制劑之共同投與的情況下向該受試者投與如請求項140-144中任一項所述之組成物進行誘導之前及之後利用脾細胞中IFNγ產生程度來評估免疫活化，其中若該受試者之該等脾細胞中之該IFNγ產生程度相較於在該組成物之該投與之前該受試者之該等脾細胞中之該IFNγ產生程度增加達至少10%、至少20%、至少30%、至少40%、至少50%、至少100%或至少200%，則該抑制劑及如請求項140-144中任一項所述之組成物向該受試者之共同投與繼續，其中若該受試者之該等脾細胞中之該IFNγ產生程度不增加，則中斷該抑制劑及如請求項140-144中任一項所述之組成物之共同投與，或在重複將如請求項140-144中任一項所述之組成物投與至該受試者之後重新分析。A companion diagnostic method for tumor therapy using an immune checkpoint inhibitor, the method comprising the steps of administering to the subject with or without co-administration of the inhibitor as requested The composition according to any one of items 140 to 144 is used to evaluate the immune activation using the degree of IFNγ production in spleen cells before and after induction, wherein if the degree of IFNγ production in the spleen cells of the subject is compared to The degree of production of the IFNγ in the splenocytes of the subject before the administration of the composition is increased by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 100% or At least 200%, the co-administration of the inhibitor and the composition as described in any one of claims 140-144 to the subject continues, wherein if the IFNγ in the spleen cells of the subject If the production level does not increase, the co-administration of the inhibitor and the composition according to any one of claims 140 to 144 is discontinued, or the composition according to any one of claims 140 to 144 is repeated Reanalyze after administration to the subject. 如請求項188所述之方法，其進一步包含以下步驟利用該特異性抗體或該MHC單體集合體分析脾細胞中之療法標靶之腫瘤抗原的表現位準。The method according to claim 188, further comprising the step of analyzing the expression level of a tumor antigen of a therapeutic target in splenocytes using the specific antibody or the MHC monomer assembly. 如請求項188所述之方法，其用於利用一免疫查核點抑制劑之腫瘤療法，其中該腫瘤抑制劑為一PD-1抑制劑、PD-L1抑制劑或CTLA-4抑制劑。The method of claim 188, for use in a tumor therapy using an immune checkpoint inhibitor, wherein the tumor inhibitor is a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor. 如請求項188所述之方法，其進一步包含以下步驟評定該受試者之T細胞中的PD-1表現。The method of claim 188, further comprising the step of assessing PD-1 expression in T cells of the subject. 如請求項188所述之方法，其進一步包含以下步驟檢查該受試者之癌細胞中的PD-L1表現。The method of claim 188, further comprising the step of checking PD-L1 expression in a cancer cell of the subject. 如請求項188所述之方法，其進一步包含以下步驟評定該受試者之T細胞中的CTLA-4表現。The method of claim 188, further comprising the step of assessing CTLA-4 performance in T cells of the subject. 一種用於進行如請求項185-193中任一項所述之伴隨式診斷方法的套組， 該套組包含一或多種IFNγ標誌物分子。A kit for performing a concomitant diagnostic method according to any one of claims 185-193, the kit comprising one or more IFNγ marker molecules. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、梭桿菌屬、多利擬桿菌、細菌IARFR67、瘤胃菌科細菌、Paraprevotella xylaniphila、約氏副擬桿菌、擬桿菌屬、戈登副擬桿菌、黏真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌、擬桿菌屬、毛螺旋菌科細菌HGA0140、Hungatella hathewayi、拉瓦梭菌、瘤胃球菌屬及無害芽胞梭菌。A composition comprising a purified bacterial mixture, the purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Fusobacterium, Bacterial doris, bacteria IARFR67, rumen bacteria Bacteria, Paraprevotella xylaniphila, Bacteroides yojei, Bacteroides, B. gordonii, Pseudomonas myxobacteria, B. dickensii, B. cellulolyticus, B. cladii, Anaerobic corynebacterium, Bacteroides selenoides, Bacteroides fragile, Bacteroides escherichia, Clostridium, B. archaebacterium, Bacteroides, Trichophytons HGA0140, Hungatella hathewayi, Clostridium lavas, Rumen Cocci and harmless Clostridium. 如請求項195所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種、至少21種、至少22種、至少23種、至少24種、至少25種或至少26種細菌菌株。The composition according to claim 195, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten At least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, At least 23, at least 24, at least 25, or at least 26 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、梭桿菌屬、多利擬桿菌、細菌IARFR67、瘤胃菌科細菌、Paraprevotella xylaniphila、約氏副擬桿菌、擬桿菌屬、戈登副擬桿菌、黏液真桿菌、狄氏副擬桿菌、解纖維素擬桿菌、克拉氏擬桿菌、糞厭氧棒狀菌、塞爾氏擬桿菌、脆弱擬桿菌、單形擬桿菌、埃氏擬桿菌、梭菌屬、古氏副擬桿菌及擬桿菌屬。A composition comprising a purified bacterial mixture, the purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Fusobacterium, Bacterial doris, bacteria IARFR67, rumen bacteria Bacteria, Paraprevotella xylaniphila, Bacteroides yojei, Bacteroides, B. gordonii, E. myxobacteria, B. dickii, B. cellulolyticus, B. clarkii, Anaerobic corynebacterium, Bacteroides selenoides, B. fragile, B. monomorphe, B. escherichia, Clostridium, B. parvii and Bacteroides. 如請求項197所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種、至少11種、至少12種、至少13種、至少14種、至少15種、至少16種、至少17種、至少18種、至少19種、至少20種或至少21種細菌菌株。The composition according to claim 197, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、梭桿菌屬、多利擬桿菌、細菌IARFR67、瘤胃菌科細菌、Paraprevotella xylaniphila、約氏副擬桿菌、擬桿菌屬、戈登副擬桿菌、黏液真桿菌及狄氏副擬桿菌。A composition comprising a purified bacterial mixture, the purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Fusobacterium, Bacterial doris, bacteria IARFR67, rumen bacteria Bacteria, Paraprevotella xylaniphila, Bacteroides yojei, Bacteroides, B. gordonii, Eumycobacterium myxoides, and B. dickii. 如請求項199所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種、至少10種或至少11種細菌菌株。The composition according to claim 199, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten Species or at least 11 strains of bacteria. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：糞考拉桿菌、梭桿菌屬、瘤胃菌科細菌及黏液真桿菌。A composition comprising a purified bacterial mixture, the purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Koala faecalis, Clostridium, rumenaceous bacteria, and Eumyxomyces mucous. 如請求項201所述之組成物，其中該純化細菌混合物包含至少2種、至少3種或至少4種細菌菌株。The composition of claim 201, wherein the purified bacterial mixture comprises at least two, at least three, or at least four bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含選自由以下各項組成之群的物種之一或多種細菌菌株：多利擬桿菌、細菌IARFR67、Paraprevotella xylaniphila、約氏副擬桿菌、擬桿菌屬、戈登副擬桿菌及狄氏副擬桿菌。A composition comprising a purified bacterial mixture, the purified bacterial mixture comprising one or more bacterial strains selected from the group consisting of: Bacterial doris, Bacteria IARFR67, Paraprevotella xylaniphila, Bacteroides yojei, Bacteroides Genus, Parabacter gordonii and Parabacillus dichii. 如請求項203所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種或至少7種細菌菌株。The composition of claim 203, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, or at least seven bacterial strains. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含： 1) 糞考拉桿菌或考拉桿菌屬CAG:207；2) 潰瘍梭桿菌或可變梭桿菌；3) 多利擬桿菌或福魯克斯擬桿菌，4) 單形擬桿菌或擬桿菌屬D20，5) 罕見小球菌屬、Ruthenibacterium lactatiformans、瘤胃菌科細菌cv2或Gemminger formicilis，6) Paraprevotella xylaniphila，7) 約氏副擬桿菌，8) 別樣桿菌屬、替莫尼斯別樣桿菌或塞內加爾別樣桿菌，9) 戈登副擬桿菌或副擬桿菌屬HGS0025，10) 黏液真桿菌，及11) 副擬桿菌屬CAG:2或狄氏副擬桿菌。A composition comprising a purified bacterial mixture comprising: 1) Koala faecalis or Koala spp. CAG: 207; 2) Clostridium ulcerans or Clostridium mutans; 3) Bacteroides doryli or Fru Bacteroides spp., 4) Bacteroides spp. Or B20, 5) Rare micrococcus, Ruthenibacterium lactatiformans, ruminal bacteria cv2 or Gemminger formicilis, 6) Paraprevotella xylaniphila, 7) Parabacter yojei, 8 ) Bacteroides, Temomonis or Bacteroides senegal, 9) Gordon or Bacteroides HGS0025, 10) Eumycobacterium myxoids, and 11) CAG: 2 or Di Paracoccus 一種包含一純化細菌混合物之組成物，該純化細菌混合物由以下各項組成： 1) 糞考拉桿菌或考拉桿菌屬CAG:207；2) 潰瘍梭桿菌或可變梭桿菌；3) 多利擬桿菌或福魯克斯擬桿菌，4) 單形擬桿菌或擬桿菌屬D20，5) 罕見小球菌屬、Ruthenibacterium lactatiformans、瘤胃菌科細菌cv2或Gemminger formicilis，6) Paraprevotella xylaniphila，6 7) 約氏副擬桿菌，8) 別樣桿菌屬、替莫尼斯別樣桿菌或塞內加爾別樣桿菌，9) 戈登副擬桿菌或副擬桿菌屬HGS0025，10) 黏液真桿菌，及11) 副擬桿菌屬CAG:2或狄氏副擬桿菌。A composition comprising a purified bacterial mixture consisting of: 1) Koala faecalis or Koala bacterium CAG: 207; 2) Clostridium ulcer or Clostridium mutans; 3) Dolomid Bacillus or B. fuchsii, 4) Bacteroides or Bacteroides D20, 5) Rare micrococcus, Ruthenibacterium lactatiformans, ruminal bacteria cv2 or Gemminger formicilis, 6) Paraprevotella xylaniphila, 6 7) Paramycobacteria, 8) Pseudomonas spp., Timmonis or Pseudomonas senegalensis, 9) Pseudomonas gordonii or P. parasiticus HGS0025, 10) Eumycobacterium myxoides, and 11) Pseudomonas CAG: 2 or B. dickii. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10或SEQ ID NO:11。A composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity with the following: SEQ ID NO: 1 , SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11. 如請求項207所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。The composition of claim 207, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten A bacterial strain. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含兩種或更多種細菌菌株，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。A composition comprising a purified bacterial mixture comprising two or more bacterial strains comprising a 16S rDNA sequence having at least 97% sequence identity with the following: SEQ ID NO: 54 , SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63 or SEQ ID NO: 64. 如請求項209所述之組成物，其中該純化細菌混合物包含至少2種、至少3種、至少4種、至少5種、至少6種、至少7種、至少8種、至少9種或至少10種細菌菌株。The composition of claim 209, wherein the purified bacterial mixture comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten A bacterial strain. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含： 包含與SEQ ID NO:1具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:2具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:3具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:4具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:5具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:6具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:7具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:8具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:9具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:10具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，及包含與SEQ ID NO:11具有至少97%序列一致性之一16S rDNA序列的一細菌菌株。A composition comprising a purified bacterial mixture comprising: a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 1, comprising a bacterial strain having at least 97 sequences with SEQ ID NO: 2 A bacterial strain with a 16S rDNA sequence of one of the% sequence identity, comprising a bacterial strain with a 16S rDNA sequence of at least 97% of the sequence identity with SEQ ID NO: 3, comprising at least 97% of a sequence with the SEQ ID NO: 4 A bacterial strain of 16S rDNA sequence of one identity, comprising a bacterial strain of 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 5, comprising of at least 97% sequence identity to SEQ ID NO: 6 A bacterial strain of one 16S rDNA sequence, comprising a bacterial strain having at least 97% sequence identity to SEQ ID NO: 7, a bacterial strain of one 16S rDNA sequence comprising at least 97% sequence identity to SEQ ID NO: 8 A bacterial strain of 16S rDNA sequence comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 9, a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 10 A bacterial strain of the sequence, and Comprising the SEQ ID NO: 11 having a bacterial strain of one of at least 97% sequence identity to 16S rDNA sequences. 一種包含一純化細菌混合物之組成物，該純化細菌混合物包含： 包含與SEQ ID NO:54具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:55具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:56具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:57具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:58具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:59具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:60具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:61具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:62具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:63具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，及包含與SEQ ID NO:64具有至少97%序列一致性之一16S rDNA序列的一細菌菌株。A composition comprising a purified bacterial mixture comprising: a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 54, comprising a bacterial strain having at least 97 sequences with SEQ ID NO: 55 A bacterial strain with a 16S rDNA sequence of one of the% sequence identity, comprising a bacterial strain having a 16S rDNA sequence of at least 97% with the sequence identity of SEQ ID NO: 56, comprising at least 97% of a sequence with the SEQ ID NO: 57 A bacterial strain with a 16S rDNA sequence that includes at least 97% sequence identity with SEQ ID NO: 58, a bacterial strain with a 16S rDNA sequence that contains at least 97% sequence identity with SEQ ID NO: 59 A 16S rDNA sequence of a bacterial strain comprising at least 97% sequence identity with SEQ ID NO: 60 A 16S rDNA sequence of a bacterial strain comprising at least 97% sequence identity with SEQ ID NO: 61 A bacterial strain of 16S rDNA sequence comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 62, a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 63 Bacteria , And comprising SEQ ID NO: one of the 16S rDNA sequence identity of at least 97% sequence 64 having a bacterial strain. 一種包含一純化細菌混合物之組成物，該純化細菌混合物由細菌菌株組成，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10及SEQ ID NO:11。A composition comprising a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with the following: SEQ ID NO: 1, SEQ ID NO: 2.SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11. 一種包含一純化細菌混合物之組成物，該純化細菌混合物由細菌菌株組成，該等細菌菌株包含與以下各項具有至少97%序列一致性之16S rDNA序列：SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63或SEQ ID NO:64。A composition comprising a purified bacterial mixture consisting of a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with the following: SEQ ID NO: 54, SEQ ID NO: 55.SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63 or SEQ ID NO: 64. 一種包含一純化細菌混合物之組成物，該純化細菌混合物由以下各項組成 包含與SEQ ID NO:1具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:2具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:3具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:4具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:5具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:6具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:7具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:8具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:9具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:10具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，及包含與SEQ ID NO:11具有至少97%序列一致性之一16S rDNA序列的一細菌菌株。A composition comprising a purified bacterial mixture consisting of the following: a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 1, comprising a bacterial strain identical to SEQ ID NO: 2 A bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, comprising a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 3, comprising a bacterial strain having at least 97% sequence identity with SEQ ID NO: 4 A bacterial strain with a 16S rDNA sequence having at least 97% sequence identity, comprising a bacterial strain with a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 5, comprising at least 97% with SEQ ID NO: 6 A bacterial strain having a sequence identity of 16S rDNA sequence comprising at least 97% sequence identity with SEQ ID NO: 7, a bacterial strain comprising at least 97% sequence identity with at least 97% sequence identity with SEQ ID NO: 7 A bacterial strain with a 16S rDNA sequence that includes at least 97% sequence identity with SEQ ID NO: 9, a bacterial strain with a 16S rDNA sequence that has at least 97% sequence identity with SEQ ID NO: 9 A 16S rDNA sequence of a bacterium Strain, and comprising SEQ ID NO: 11 having a bacterial strain of one of at least 97% sequence identity to 16S rDNA sequences. 一種包含一純化細菌混合物之組成物，該純化細菌混合物由以下各項組成 包含與SEQ ID NO:54具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:55具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:56具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:57具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:58具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:59具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:60具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:61具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:62具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，包含與SEQ ID NO:63具有至少97%序列一致性之一16S rDNA序列的一細菌菌株，及包含與SEQ ID NO:64具有至少97%序列一致性之一16S rDNA序列的一細菌菌株。A composition comprising a purified bacterial mixture consisting of the following: a bacterial strain comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 54, comprising a bacterial strain identical to SEQ ID NO: 55 A bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, comprising a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity to SEQ ID NO: 56, comprising a bacterial strain having at least 97% sequence identity with SEQ ID NO: 57 A bacterial strain having a 16S rDNA sequence having at least 97% sequence identity, comprising a bacterial strain having a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 58, comprising at least 97% having a sequence identity with SEQ ID NO: 59 A bacterial strain with a sequence identity of 16S rDNA sequence comprising a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 60 and a bacterial strain comprising at least 97% sequence identity with SEQ ID NO: 61 A bacterial strain with a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 62, a bacterial strain with a 16S rDNA sequence having at least 97% sequence identity with SEQ ID NO: 63 A 16S rDNA sequence Bacterial strain, and comprises SEQ ID NO: 64 having a bacterial strain of one of at least 97% sequence identity to 16S rDNA sequences. 如請求項137-144或195-216中任一項所述之組成物，其中該組成物為一醫藥組成物。The composition according to any one of claims 137-144 or 195-216, wherein the composition is a pharmaceutical composition. 如請求項217所述之醫藥組成物，其中該醫藥組成物包含一醫藥學上可接受的賦形劑。The pharmaceutical composition according to claim 217, wherein the pharmaceutical composition comprises a pharmaceutically acceptable excipient. 如請求項218所述之醫藥組成物，其中該醫藥組成物係配製用於口服投與。The pharmaceutical composition according to claim 218, wherein the pharmaceutical composition is formulated for oral administration. 如請求項218或請求項219所述之醫藥組成物，其中該醫藥組成物係配製用於直腸投與。The pharmaceutical composition according to claim 218 or claim 219, wherein the pharmaceutical composition is formulated for rectal administration. 如請求項218-220中任一項所述之醫藥組成物，其中該醫藥組成物係配製用於遞送至腸。The pharmaceutical composition of any one of claims 218-220, wherein the pharmaceutical composition is formulated for delivery to the intestine. 如請求項218-221中任一項所述之醫藥組成物，其中該醫藥組成物係配製用於遞送至結腸。The pharmaceutical composition of any one of claims 218-221, wherein the pharmaceutical composition is formulated for delivery to the colon. 如請求項218-222中任一項所述之醫藥組成物，其中該等細菌菌株之一或多者係凍乾的。The pharmaceutical composition according to any one of claims 218-222, wherein one or more of the bacterial strains are lyophilized. 如請求項218-223中任一項所述之醫藥組成物，其中該醫藥組成物係呈一膠囊形式。The pharmaceutical composition according to any one of claims 218-223, wherein the pharmaceutical composition is in the form of a capsule. 如請求項218-224中任一項所述之醫藥組成物，其中該醫藥組成物進一步包含一pH敏感組成物，該pH敏感組成物包含一或多種腸聚合物。The pharmaceutical composition according to any one of claims 218-224, wherein the pharmaceutical composition further comprises a pH-sensitive composition, and the pH-sensitive composition comprises one or more enteric polymers. 如請求項217-225中任一項所述之醫藥組成物，其中該組成物進一步包含一或多種抗癌劑。The pharmaceutical composition according to any one of claims 217-225, wherein the composition further comprises one or more anticancer agents.
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